Input: The inhibition of c-fos and c-jun expression by IL-4 in LPS-treated cells was shown to be due to a lower transcription rate of the c-fos and c-jun genes.

c-fos

c-fos and c-jun genes

LPS-treated cells


Input: IL-4 did not affect the stability of the c-fos and c-jun transcripts.

c-fos

c-jun transcripts


Input: Finally, using electrophoretic mobility shift assays, evidence was obtained that IL-4 inhibits LPS-induced expression of AP-1 protein.


Input: These data indicate that IL-4 suppresses the induction of transcription factors in human activated monocytes.

transcription factors

human activated monocytes


Input: Transient pseudohypoaldosteronism in obstructive renal disease with transient reduction of lymphocytic aldosterone receptors.

lymphocytic aldosterone receptors


Input: Results in two affected infants.


Input: We report two patients with transient pseudohypoaldosteronism due to obstructive renal disease.


Input: Both patients presented with a salt-losing episode simulating adrenal insufficiency.


Input: In one patient, transient reduction of aldosterone receptors could be documented, while in the second patient the clinical and biochemical parameters were consistent with transient pseudohypoaldosteronism.

aldosterone receptors


Input: Aldosterone receptors were normal in both patients

Aldosterone receptors


Input: Aldosterone-specific membrane receptors and rapid non-genomic actions of mineralocorticoids.

Aldosterone-specific membrane receptors


Input: Functional studies in extrarenal, non-epithelial cells such as smooth muscle cells and more recently circulating human lymphocytes have provided increasing evidence that aldosterone produces not only classical genomic effects, but also rapid, non-genomic effects on transmembrane electrolyte movements.

extrarenal, non-epithelial cells

smooth muscle cells

circulating

human lymphocytes


Input: These involve activation of the sodium/proton exchanger of the cell membrane at very low, physiological concentrations of aldosterone with an acute onset within 1-2 min.

sodium/proton exchanger


Input: A second messenger cascade involved is the inositol 1,4,5-trisphosphate /calcium pathway which responds over the same rapid time course.


Input: Such changes clearly cannot be explained by genomic mechanisms, which are responsible for later effects than the membrane related rapid responses.


Input: The mechanisms underlying these rapid effects of aldosterone on electrolytes have been extensively studied in human lymphocytes, which thus may represent valuable tools in the delineation of the receptor-effector mechanisms involved.

human lymphocytes


Input: The unique characteristics of this new pathway for steroid action include its rapid time course, 10,000-fold selectivity for aldosterone over cortisol and the ineffectiveness of spironolactones, classical mineralocorticoid antagonists, as antagonists of the response.


Input: Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells.

Human immunodeficiency virus type 1 Nef protein

NF-kappa B

human T cells


Input: Human immunodeficiency virus type 1 (HIV-1) can establish a persistent and latent infection in CD4+ T lymphocytes (W.C.Greene, N.Engl.J. Med.324:308-317, 1991; S.M.Schnittman, M.C.Psallidopoulos, H.C. Lane, L.Thompson, M.Baseler, F.Massari, C.H.Fox, N.P.Salzman, and A.S.Fauci, Science 245:305-308, 1989).

CD4+ T lymphocytes


Input: Production of HIV-1 from latently infected cells requires host cell activation by T-cell mitogens (T.Folks, D.M.Powell, M.M.Lightfoote, S.Benn, M.A. Martin, and A.S.Fauci, Science 231:600-602, 1986; D.Zagury, J. Bernard, R.Leonard, R.Cheynier, M.Feldman, P.S.Sarin, and R.C. Gallo, Science 231:850-853, 1986).

T-cell mitogens


Input: This activation is mediated by the host transcription factor NF-kappa B [G.Nabel and D.Baltimore, Nature (London) 326:711-717, 1987].

host transcription factor

NF-kappa B


Input: We report here that the HIV-1 -encoded Nef protein inhibits the induction of NF-kappa B DNA-binding activity by T- cell mitogens.

HIV-1 -encoded Nef protein

NF-kappa B

T- cell mitogens


Input: However, Nef does not affect the DNA-binding activity of other transcription factors implicated in HIV-1 regulation, including SP-1, USF, URS, and NF-AT.

Nef

transcription factors

USF

URS

NF-AT


Input: Additionally, Nef inhibits the induction of HIV-1- and interleukin 2- directed gene expression, and the effect on HIV-1 transcription depends on an intact NF-kappa B -binding site.

Nef

NF-kappa B -binding site


Input: These results indicate that defective recruitment of NF-kappa B may underlie Nef's negative transcriptional effects on the HIV-1 and interleukin 2 promoters.

NF-kappa B

Nef


Input: Further evidence suggests that Nef inhibits NF-kappa B induction by interfering with a signal derived from the T-cell receptor complex.

Nef

NF-kappa B

T-cell receptor complex


Input: Expression of c-fos, c-jun and jun B in peripheral blood lymphocytes from young and elderly adults.

c-fos

c-jun

jun B


Input: The expression of c-fos, c-jun and jun B proto-oncogenes was studied in phytohemagglutinin (PHA) activated peripheral blood lymphocytes (PBL) from young and aged humans.

phytohemagglutinin

(PHA) activated peripheral blood lymphocytes

PBL


Input: Specific mRNAs for c-fos and c-jun were detectable within 30 min after cell activation and reached maximal levels within 2 h.

mRNAs

c-fos

c-jun


Input: Both c-fos and jun B mRNAs decreased to pre-activation levels within 6 h, while c-jun mRNA remained elevated.

c-fos and

jun B mRNAs

c-jun mRNA


Input: In PHA -activated PBL, no age-related differences were observed in c-fos or jun B mRNA expression.

PHA

-activated PBL


Input: However, c-jun mRNA levels decreased significantly (1.73 +/- 0.08 vs. 1.16 +/- 0.09 arbitrary units, P < 0.01, young vs. old) in PBL from elderly individuals activated with PHA.

c-jun mRNA

PBL

PHA


Input: Because previous work has demonstrated that T cells from elderly individuals may display normal proliferative responses when activated via the anti-CD2 pathway, c-jun and jun B mRNA expression was also studied in anti-CD2-activated purified T cells.

T cells

anti-CD2-activated purified T cells


Input: No age-related differences were found in the expression of either of these two proto-oncogenes by anti-CD2 activated T cells.

proto-oncogenes


Input: These results suggest that the decreased IL-2 production and proliferative response displayed by PHA -activated PBL from elderly adults may be related to age-related changes in c-jun mRNA expression and in the ratio of c-fos to c-jun mRNA.

PHA

-activated PBL

c-jun

mRNA

c-fos

c-jun mRNA


Input: Oct2 transactivation from a remote enhancer position requires a B-cell-restricted activity.

remote enhancer position


Input: Previous cotransfection experiments had demonstrated that ectopic expression of the lymphocyte-specific transcription factor Oct2 could efficiently activate a promoter containing an octamer motif.

lymphocyte-specific transcription factor

promoter

octamer motif


Input: Oct2 expression was unable to stimulate a multimerized octamer enhancer element in HeLa cells, however.

multimerized octamer enhancer element

HeLa cells


Input: We have tested a variety of Oct2 isoforms generated by alternative splicing for the capability to activate an octamer enhancer in nonlymphoid cells and a B-cell line.

Oct2 isoforms

octamer enhancer

nonlymphoid cells

B-cell line


Input: Our analyses show that several Oct2 isoforms can stimulate from a remote position but that this stimulation is restricted to B cells.

Oct2 isoforms

B cells


Input: This result indicates the involvement of either a B-cell-specific cofactor or a specific modification of a cofactor or the Oct2 protein in Oct2 -mediated enhancer activation.

B-cell-specific cofactor

cofactor

Oct2 protein


Input: Mutational analyses indicate that the carboxy-terminal domain of Oct2 is critical for enhancer activation.

carboxy-terminal domain


Input: Moreover, this domain conferred enhancing activity when fused to the Oct1 protein, which by itself was unable to stimulate from a remote position.

Oct1 protein


Input: The glutamine-rich activation domain present in the amino-terminal portion of Oct2 and the POU domain contribute only marginally to the transactivation function from a distal position.

glutamine-rich activation domain

amino-terminal portion of Oct2

POU domain


Input: The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP.

promoter

CD19 gene

B-cell-specific transcription factor

BSAP


Input: The CD19 protein is expressed on the surface of all B-lymphoid cells with the exception of terminally differentiated plasma cells and has been implicated as a signal-transducing receptor in the control of proliferation and differentiation.

CD19 protein

B-lymphoid cells

terminally differentiated plasma cells


Input: Here we demonstrate complete correlation between the expression pattern of the CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B-lymphoid cell lines.

CD19 gene

B-cell-specific transcription factor

BSAP

B-lymphoid cell lines


Input: The human CD19 gene has been cloned, and several BSAP -binding sites have been mapped by in vitro protein-DNA binding studies.

human

CD19 gene

-binding sites

BSAP


Input: In particular, a high-affinity BSAP-binding site instead of a TATA sequence is located in the -30 promoter region upstream of a cluster of heterogeneous transcription start sites.

high-affinity BSAP-binding site

TATA sequence

-30 promoter region

heterogeneous transcription start sites


Input: Moreover, this site is occupied by BSAP in vivo in a CD19-expressing B-cell line but not in plasma or HeLa cells.

BSAP

B-cell line

HeLa cells

plasma


Input: This high-affinity site has been conserved in the promoters of both human and mouse CD19 genes and was furthermore shown to confer B-cell specificity to a beta-globin reporter gene in transient transfection experiments.

high-affinity site

promoters


Input: In addition, BSAP was found to be the only abundant DNA-binding activity of B-cell nuclear extracts that interacts with the CD19 promoter.

BSAP

CD19 promoter


Input: Together, this evidence strongly implicates BSAP in the regulation of the CD19 gene.

BSAP

CD19 gene


Input: Eicosanoids in breast cancer patients before and after mastectomy.


Input: In 19 patients with a malignant breast tumor, tumor tissue and blood were taken to determine the eicosanoid profile and platelet aggregation.

platelet


Input: Values were compared with those of patients with benign tumors (n = 4), or undergoing a mammary reduction (n = 7).


Input: Postoperatively, blood was taken as well in order to compare pre- and postoperative values.


Input: Eicosanoids were measured in peripheral blood monocytes and mammary tissue by means of HPLC; furthermore, TXA2, 6-keto-PGF1 alpha, and PGE2 were determined by RIA.

peripheral blood monocytes


Input: Differences in pre- and postoperative values of cancer patients were seen in plasma RIA values: PGE2 and 6-k-PGF1 alpha were significantly higher preoperatively when compared with postoperatively, however, such differences were seen in the control groups as well.


Input: Compared to benign tumor or mammary reduction test material the eicosanoid profile of tissue obtained from malignant mammary tumors showed important differences.


Input: Except for PGF2 alpha, HHT and 15-HETE no detectable quantities of eicosanoids were found in the non-tumor material, whereas in the malignant tumor material substantial quantities of a number of eicosanoid metabolites were present.


Input: Statistically significant correlations could be established between patient/histopathology data and the results of the platelet aggregation assays, e.g. between menopausal status and ADP aggregation; oestrogen receptor (+/-) and collagen and arachidonic acid aggregation, inflammatory cell infiltration score and arachidonic acid aggregation and fibrosis score and ADP aggregation.

platelet

oestrogen receptor

collagen


Input: The results show that eicosanoid synthesis in material from mammary cancer patients is different from that in benign mammary tissue.


Input: The implications, in particular, in relation to future prognosis of the patient, remain obscure.


Input: Mineralocorticoids and mineralocorticoid receptors in mononuclear leukocytes in patients with pregnancy-induced hypertension.

mineralocorticoid receptors

mononuclear leukocytes


Input: To examine the role of mineralocorticoids in the pathophysiology of pregnancy-induced hypertension (PIH ), we studied plasma aldosterone and 18-hydroxycorticosterone levels in 25 women with PIH and 25 normal pregnant women, as controls.


Input: Furthermore, we evaluated the mineralocorticoid receptor (MR) status in mononuclear leukocytes in the 2 groups.

mineralocorticoid receptor

MR

mononuclear leukocytes


Input: MR count was significantly (P less than 0.0005) decreased in the PIH group (148 +/- 9 binding sites/cell) compared with the control group (300 +/- 17 binding sites/cell; mean +/- SEM).

MR


Input: Plasma aldosterone in women with PIH was 281 +/- 61 pmol/L; in normal pregnant women it was 697 +/- 172 pmol/L (P less than 0.025).


Input: Plasma 18-hydroxycorticosterone was also significantly (P less than 0.025) lower (PIH, 1071 +/- 149 pmol/L; controls, 1907 +/- 318 pmol/L).


Input: These values were determined at the onset of clinical symptoms of PIH.


Input: These results cannot be explained by receptor down-regulation due to higher levels of mineralocorticoids in PIH; a hitherto unknown mineralocorticoid may, thus, be responsible for the hypertension and altered MR status.

MR


Input: Structure function analysis of vitamin D analogs with C-ring modifications.


Input: Analogs of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) with substitutions on C-11 were synthesized.


Input: Small apolar substitutions (11 alpha-methyl, 11 alpha-fluoromethyl) did not markedly decrease the affinity for the vitamin D receptor, but larger (11 alpha-chloromethyl or 11 alpha- or 11 beta-phenyl) or more polar substitutions (11 alpha-hydroxymethyl, 11 alpha-(2-hydroxyethyl] decreased the affinity to less than 5% of that of 1 alpha,25-OH)2D3.

vitamin D receptor


Input: Their affinity for the vitamin D -binding protein, however, increased up to 4-fold.

vitamin D -binding protein


Input: The biological activity of 11 alpha-methyl-1 alpha,25-(OH)2D3 closely resembled that of the natural hormone on normal and leukemic cell proliferation and bone resorption, whereas its in vivo effect on calcium metabolism of the rachitic chick was about 50% of that of 1 alpha,25-(OH)2D3.

leukemic cell


Input: The 11 beta-methyl analog had a greater than 10-fold lower activity.


Input: The differentiating effects of the other C-11 analogs on human promyeloid leukemia cells (HL-60) agreed well with their bone-resorbing activity and receptor affinity, but they demonstrated lower calcemic effects in vivo.

human promyeloid leukemia cells


Input: Large or polar substitutions on C-11 of 1 alpha,25-(OH)2D3 thus impair the binding of the vitamin D receptor but increase the affinity to vitamin D-binding protein.

vitamin D receptor

vitamin D-binding protein


Input: The effects of many C-11-substituted 1 alpha,25-(OH)2D3 analogs on HL-60 cell differentiation exceeded their activity on calcium metabolism.


Input: Glucocorticoid receptor binding in three different cell types in major depressive disorder: lack of evidence of receptor binding defect.

Glucocorticoid receptor


Input: In order to further understand the apparent glucocorticoid resistance in major depressive disorder, circadian variation in cortisol concentration, dexamethasone suppression and glucocorticoid receptor binding in mononuclear leukocytes, polymorphonuclear leukocytes and cultured skin fibroblasts were measured in rigidly defined major depressive disorder patients and non-depressed psychiatric controls.

mononuclear leukocytes

polymorphonuclear leukocytes

cultured skin fibroblasts


Input: Mononuclear leukocytes binding to glucocorticoid correlated significantly with polymorphonuclear leukocytes binding to glucocorticoid, but both determinations failed to differentiate major depressive disorder and control subjects.

Mononuclear leukocytes

polymorphonuclear leukocytes


Input: Initial and post- dexamethasone in vitro fibroblast binding to glucocorticoid was not different between major depressive disorder and non-depressed control subjects.


Input: The phenomenon of glucocorticoid resistance in major depressive disorder remains unexplained.


Input: High affinity aldosterone binding to plasma membrane rich fractions from mononuclear leukocytes: is there a membrane receptor for mineralocorticoids?

mononuclear leukocytes

membrane receptor


Input: In vitro effects of aldosterone on the intracellular concentrations of sodium, potassium and calcium, cell volume and the sodium -proton-antiport have been described in intact human mononuclear leukocytes (HML ).

sodium -proton-antiport

human mononuclear leukocytes

HML


Input: In the present paper, the binding of a [125I]-labeled aldosterone derivative to plasma membrane rich fractions of HML was studied.

HML


Input: High affinity binding of the radioligand with an apparent Kd of approximately 0.1 nM was found.


Input: Aldosterone displaced the tracer at a similar Kd.


Input: Both canrenone and cortisol were inactive as ligands up to concentrations of 0.1 microM.


Input: The findings are the first to demonstrate membrane binding sites with a high affinity for aldosterone, but not for cortisol.


Input: These data are perfectly compatible with major properties of steroidal effects on the sodium-proton-antiport in HML and thus very likely represent membrane receptors for aldosterone.

sodium-proton-antiport

membrane receptors

HML


Input: Natural variants of the HIV-1 long terminal repeat: analysis of promoters with duplicated DNA regulatory motifs.

HIV-1 long terminal repeat

promoters

DNA regulatory motifs


Input: Sequence variation in the long terminal repeat (LTR) region of HIV-1 was analyzed in viral isolates of 17 infected individuals.

long terminal repeat (LTR) region


Input: Two classes of LTR size variants were found.


Input: One HIV-1 variant was detected containing an additional binding site for the transcription factor Sp1.


Input: Another LTR size variation was observed in four patients in a region just upstream of the NF-kappa B enhancer.

LTR size variation

NF-kappa B enhancer


Input: This variation was the result of a duplication of a short DNA sequence (CTG-motif ).

short DNA sequence

CTG-motif


Input: Cell culture experiments demonstrated that the natural variant with four Sp1 sites had a slightly higher promoter activity and viral replication rate than the isogenic control LTR with three Sp1 sites.

Sp1 sites

isogenic control LTR

sites


Input: No positive effect of the duplicated CTG-motif could be detected.

CTG-motif


Input: In order to measure small differences in virus production more accurately, equal amounts of a size variant and the wild-type plasmid were cotransfected into T-cells.

wild-type plasmid

T-cells


Input: The virus with four Sp1 sites did outgrow the three Sp1 virus in 35 days of culture and CTG-monomer virus outcompeted the CTG-dimer virus in 42 days.


Input: Based on these results we estimate a 5-10% difference in virus production of the LTR variants when compared to that of wild-type.

LTR variants


Input: A novel B cell-derived coactivator potentiates the activation of immunoglobulin promoters by octamer-binding transcription factors.

novel B cell-derived coactivator

octamer-binding transcription factors

immunoglobulin promoters


Input: A novel B cell-restricted activity, required for high levels of octamer / Oct -dependent transcription from an immunoglobulin heavy chain (IgH) promoter, was detected in an in vitro system consisting of HeLa cell -derived extracts complemented with fractionated B cell nuclear proteins.

octamer

Oct

immunoglobulin heavy chain (IgH) promoter

HeLa cell

fractionated B cell nuclear proteins


Input: The factor responsible for this activity was designated Oct coactivator from B cells (OCA-B ).

Oct coactivator

OCA-B

B cells


Input: OCA-B stimulates the transcription from an IgH promoter in conjunction with either Oct-1 or Oct-2 but shows no significant effect on the octamer / Oct -dependent transcription of the ubiquitously expressed histone H2B promoter and the transcription of USF- and Sp1- regulated promoters.

OCA-B

IgH promoter

octamer

Oct

ubiquitously expressed histone H2B promoter


Input: Taken together, our results suggest that OCA-B is a tissue-, promoter-, and factor- specific coactivator and that OCA-B may be a major determinant for B cell-specific activation of immunoglobulin promoters.

OCA-B

OCA-B

immunoglobulin promoters


Input: In light of the evidence showing physical and functional interactions between Oct factors and OCA-B, we propose a mechanism of action for OCA-B and discuss the implications of OCA-B for the transcriptional regulation of other tissue-specific promoters.

Oct factors

OCA-B

OCA-B

OCA-B

tissue-specific promoters


Input: SCL and related hemopoietic helix-loop-helix transcription factors.

SCL

hemopoietic helix-loop-helix transcription factors


Input: The helix-loop-helix (HLH) proteins are a family of transcription factors that include proteins critical to differentiation and development in species ranging from plants to mammals.

helix-loop-helix (HLH) proteins

transcription factors


Input: Five members of this family (MYC, SCL, TAL-2, LYL-1 and E2A) are implicated in oncogenic events in human lymphoid tumors because of their consistent involvement in chromosomal translocations.

MYC

SCL


Input: Although activated in T cell leukemias, expression of SCL and LYL-1 is low or undetectable in normal T cell populations.

SCL

normal T cell populations


Input: SCL is expressed in erythroid, megakaryocyte and mast cell populations (the same cell lineages as GATA-1, a zinc-finger transcription factor ).

SCL

zinc-finger transcription factor


Input: In addition, both SCL and GATA-1 undergo coordinate modulation during chemically induced erythroid differentiation of mouse erythroleukemia cells and are down-modulated during myeloid differentiation of human K562 cells, thus implying a role for SCL in erythroid differentiation events.

SCL

SCL

mouse erythroleukemia cells

human K562 cells


Input: However, in contrast to GATA-1, SCL is expressed in the developing brain.

SCL


Input: Studies of the function of SCL suggest it is also important in proliferation and self-renewal events in erythroid cells.

SCL

erythroid cells


Input: Induction of the POU domain transcription factor Oct-2 during T-cell activation by cognate antigen.

POU domain transcription factor

T-cell


Input: Oct-2 is a transcription factor that binds specifically to octamer DNA motifs in the promoters of immunoglobulin and interleukin-2 genes.

transcription factor

octamer DNA motifs

promoters


Input: All tumor cell lines from the B-cell lineage and a few from the T-cell lineage express Oct-2.

tumor cell lines

B-cell lineage

T-cell lineage


Input: To address the role of Oct-2 in the T-cell lineage, we studied the expression of Oct-2 mRNA and protein in nontransformed human and mouse T cells.

T-cell lineage

Oct-2 mRNA


Input: Oct-2 was found in CD4+ and CD8+ T cells prepared from human peripheral blood and in mouse lymph node T cells.

mouse lymph node T cells


Input: In a T-cell clone specific for pigeon cytochrome c in the context of I-Ek, Oct-2 was induced by antigen stimulation, with the increase in Oct-2 protein seen first at 3 h after activation and continuing for at least 24 h.

T-cell clone

pigeon cytochrome c

I-Ek

Oct-2 protein


Input: Oct-2 mRNA induction during antigen-driven T-cell activation was blocked by cyclosporin A, as well as by protein synthesis inhibitors.

Oct-2 mRNA

T-cell


Input: These results suggest that Oct-2 participates in transcriptional regulation during T-cell activation. The relatively delayed kinetics of Oct-2 induction suggests that Oct-2 mediates the changes in gene expression which occur many hours or days following antigen stimulation of T lymphocytes.

T-cell

T lymphocytes


Input: Glucocorticoid receptor in patients with lupus nephritis: relationship between receptor levels in mononuclear leukocytes and effect of glucocorticoid therapy.

Glucocorticoid receptor

mononuclear leukocytes


Input: We investigated the clinical significance of glucocorticoid receptor determination in 20 patients with systemic lupus erythematosus (SLE) who afterwards developed nephrotic syndrome.

glucocorticoid receptor


Input: Glucocorticoid receptor concentrations in mononuclear leukocytes (MNL) in these patients were comparable with those in both other patients with SLE and healthy persons.

Glucocorticoid receptor

mononuclear leukocytes

MNL


Input: Improvement in urinary protein excretion and in disease activity, which was scored according to the SLE Disease Activity Index system of the University of Toronto, closely related to the glucocorticoid receptor concentrations in MNL isolated from the corresponding patients.

glucocorticoid receptor

MNL


Input: In summary, glucocorticoid receptor determination in patients with lupus nephritis may be a predictive clue for assessing responsiveness to glucocorticoid therapy.

glucocorticoid receptor


Input: [Changes in plasma interleukin-1 and their possible relationship with the changes in glucocorticoid receptor in aged long-distance runner]

plasma interleukin-1

glucocorticoid receptor


Input: For the study of the changes in plasma interleukin-1 (IL-1) and their possible relationship with the changes in glucocorticoid receptor (GR ), plasma IL-1 and GR in peripheral blood leukocytes in aged long-distance runner were measured simultaneously.

plasma interleukin-1

glucocorticoid receptor

GR

plasma

GR

peripheral blood leukocytes


Input: The activity of IL-1 was expressed as its ability to stimulate 3H-TdR incorporation in the thymocytes of C57 mice.

thymocytes


Input: GR was determined by whole cell assay with 3H-Dex.

GR


Input: The results showed that the activity of plasma IL-1 in aged long-distance runner was 209%, 223% and 145% of the control at 14.7-18.7, 3.8-7.0 and 1.5-2.6 KD fractions.


Input: The GR in peripheral blood leukocytes in aged runner was 65% of the control.

GR

peripheral blood leukocytes


Input: Possible relationship between the changes in IL-1 and GR in aged long-distance runner and its physiological significance are discussed.

GR


Input: Mineralocorticoid effector mechanism in preeclampsia.


Input: Mineralocorticoid effector mechanisms were evaluated in 29 patients with preeclampsia and in 25 uncomplicated pregnancies by measurement of plasma aldosterone, levels of mineralocorticoid receptor (MR) in mononuclear leucocytes, and subtraction potential difference (SPD; rectal minus oral values ).

mineralocorticoid receptor

MR

mononuclear leucocytes


Input: Mean values for plasma aldosterone were not different between the two groups, but significant differences were observed for MR (preeclampsia, 81 +/- 44 receptors/cell; controls, 306 +/- 168) and SPD (preeclampsia, 65 +/- 7 mV; controls, 12 +/- 5 mV).

MR


Input: In six cases we determined MR, plasma aldosterone, and SPD in patients with preeclampsia before and 3 months after delivery.

MR


Input: MR were reduced before delivery (96 +/- 27 receptors/cell), and SPD increased (64 +/- 8 mV), with both parameters normalizing after delivery (MR, 242 +/- 79; SPD, 14.0 +/- 4 mV).

MR

MR


Input: Aldosterone levels returned to normal nonpregnant values after delivery.


Input: These data suggest an important role for abnormalities in mineralocorticoid effector mechanisms in the etiology of preeclampsia and could be an useful marker for diagnosis.


Input: Kinetics of nuclear translocation and turnover of the vitamin D receptor in human HL60 leukemia cells and peripheral blood lymphocytes --coincident rise of DNA-relaxing activity in nuclear extracts.

vitamin D receptor

human HL60 leukemia cells

peripheral blood lymphocytes


Input: High affinity receptors (VDR) for 1,25-dihydroxycholecalciferol (calcitriol) are expressed in HL60 human leukemia cells and in low numbers in peripheral blood lymphocytes (PBL ).

High affinity receptors

VDR

peripheral blood lymphocytes

PBL


Input: HL60 cells, expressing some characteristics of promyelocytes, can be induced to monocytoid differentiation by calcitriol.

HL60 cells

promyelocytes


Input: Specific nuclear translocation of [3H]calcitriol/VDR was examined after exposure of whole cells to 10(-9) M/l calcitriol in the presence and absence of a 500-fold excess of unlabeled ligand and subsequent isolation of nuclei.

whole cells


Input: Specific nuclear translocation of [3H]calcitriol/VDR was found to be time dependent reaching a maximum of approximately 2100 binding sites/nucleus after 3 h of incubation in HL60 cells, whereas a maximum of approximately 310 binding sites/nucleus was found after 3 h in PBL.

HL60 cells

PBL


Input: Pulse exposure of HL60 to radiolabeled hormone for 3 h followed by culture in medium without serum and calcitriol lead to nuclear retention of approximately 1600 radiolabeled VDR by 8 h and approximately 1000 VDR by 24 h.

1600 radiolabeled VDR

VDR


Input: Radiolabeled VDR disappeared from the nuclear compartment with a halflife of approximately 30 min if cells were cultured with identical concentrations of unlabeled hormone after the pulse (pulse/chase-experiments).

Radiolabeled

VDR


Input: No difference of VDR retention in pulse and pulse/chase-experiments was seen in PBL, where VDR halflife was approximately 30 min.

VDR

VDR

PBL


Input: No specific translocation into the nuclear compartment was seen when isolated nuclei were incubated in [3H]calcitriol.


Input: Radiolabeled hormone/receptor complexes of nuclei isolated from cells exposed for 3 h to radiolabeled hormone --in contrast to identical experiments with intact cells--did not disappear from the nuclear compartment upon incubation of nuclei with identical concentrations of the unlabeled compound.

Radiolabeled hormone/receptor complexes


Input: The activity of DNA relaxing enzymes (e.g. topoisomerases I and II) in nuclear extracts was measured using a PBR 322-relaxation-assay.

DNA relaxing enzymes


Input: Enhanced overall enzyme activity was found in nuclear extracts by 1 h after incubation with calcitriol (final ethanol concentration 0.0001% v/v) in HL60 and PBL.

PBL


Input: The enhanced activity disappeared after 2 h in PBL, whereas it was still enhanced by 4 h in HL60.

PBL


Input: No effect was seen in ethanol treated controls.

ethanol treated controls


Input: We conclude that a specific nuclear translocation mechanism exists for calcitriol in both cell types examined, most likely due to translocation of receptor proteins after hormone binding.

receptor proteins


Input: Translocated hormone/receptor complexes compete for a limited number of specific nuclear binding sites.

Translocated hormone/receptor complexes


Input: Enhanced activity of topoisomerases in nuclear extracts upon translocation of VDR might reflect interaction of both within the nuclear compartment, thus initiating DNA-unwinding, a prerequisite of transcription initiation.

topoisomerases

VDR


Input: Influence of estradiol and tamoxifen on susceptibility of human breast cancer cell lines to lysis by lymphokine-activated killer cells.

human breast cancer cell lines

lymphokine-activated killer cells


Input: The design of combination hormonal and immunotherapeutic protocols for breast cancer patients may be facilitated by analysis of preclinical in vitro model systems.


Input: Estrogen receptor positive (ER+: MCF-7) and negative (ER-: MDA-MB-231) human breast cancer cell lines were utilized to evaluate the effects of tamoxifen (TAM) and estradiol (E2) on modulation of breast cancer target susceptibility to lysis by lymphokine-activated killer (LAK) cells.

Estrogen receptor positive (ER+: MCF-7) and negative (ER-: MDA-MB-231) human breast cancer cell lines

lymphokine-activated killer (LAK) cells


Input: E2 -stimulated ER+ cells were more susceptible to lysis by LAK cells than corresponding TAM -treated or control cells, while treatment of ER- cells with either E2 or TAM alone did not alter from control their susceptibility to this immune-mediated lysis.

E2 -stimulated ER+ cells

TAM -treated

ER- cells

LAK cells

control cells


Input: All ER+ and ER- cells tested remained sensitive after treatment with TAM to lysis by LAK cells.

LAK cells


Input: In addition, an adenocarcinoma reactive human-mouse chimeric monoclonal antibody (ING-1) was able to significantly boost in vivo generated LAK cell-mediated lysis of control, E2-treated, and TAM-treated ER+ and ER- cells.

adenocarcinoma reactive human-mouse chimeric monoclonal antibody


Input: These in vitro results provide a preclinical rationale for in vivo testing of TAM, interleukin-2 (IL-2 ), and breast cancer reactive antibody-dependent cellular cytotoxicity facilitating antibody in patients with refractory or high risk breast cancer.


Input: The cellular oncogene c-myb can interact synergistically with the Epstein-Barr virus BZLF1 transactivator in lymphoid cells.

cellular oncogene

c-myb

Epstein-Barr virus BZLF1 transactivator

lymphoid cells


Input: Regulation of replicative functions in the Epstein-Barr virus (EBV) genome is mediated through activation of a virally encoded transcription factor, Z (BZLF1 ).

Epstein-Barr virus (EBV) genome

virally encoded transcription factor

Z


Input: We have shown that the Z gene product, which binds to AP-1 sites as a homodimer and has sequence similarity to c-Fos, can efficiently activate the EBV early promoter, BMRF1, in certain cell types (i.e., HeLa cells) but not others (i.e., Jurkat cells ).

Z gene product

homodimer

AP-1 sites

c-Fos

EBV early promoter

HeLa cells

Jurkat cells


Input: Here we demonstrate that the c-myb proto-oncogene product, which is itself a DNA-binding protein and transcriptional transactivator, can interact synergistically with Z in activating the BMRF1 promoter in Jurkat cells (a T-cell line) or Raji cells (an EBV -positive B-cell ), whereas the c-myb gene product by itself has little effect.

c-myb

BMRF1 promoter

proto-oncogene product

DNA-binding protein

transcriptional transactivator

Z

c-myb gene product

Jurkat cells

T-cell line

Raji cells

EBV -positive B-cell


Input: The simian virus 40 early promoter is also synergistically activated by the Z/c-myb combination.

simian virus 40 early promoter

Z/c-myb combination


Input: Synergistic transactivation of the BMRF1 promoter by the Z/c-myb combination appears to involve direct binding by the Z protein but not the c-myb protein.

BMRF1 promoter

Z/c-myb combination

Z protein

c-myb protein


Input: A 30-bp sequence in the BMRF1 promoter which contains a Z binding site (a consensus AP-1 site) is sufficient to transfer high-level lymphoid-specific responsiveness to the Z/c-myb combination to a heterologous promoter.

30-bp sequence

BMRF1 promoter

Z binding site

consensus AP-1 site

heterologous promoter

Z/c-myb combination


Input: That the c-myb oncogene product can interact synergistically with an EBV -encoded member of the leucine zipper protein family suggests c-myb is likely to engage in similar interactions with cellularly encoded transcription factors.

c-myb oncogene product

EBV -encoded member

leucine zipper protein family

cellularly encoded transcription factors

c-myb


Input: Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells.

NF-kappa B

human T cells


Input: Acquired immunodeficiency syndrome (AIDS) results from infection with a human immunodeficiency virus (HIV ).


Input: The long terminal repeat (LTR) region of HIV proviral DNA contains binding sites for nuclear factor kappa B (NF-kappa B ), and this transcriptional activator appears to regulate HIV activation.

long terminal repeat (LTR) region

HIV proviral DNA

nuclear factor kappa B

NF-kappa B

transcriptional activator


Input: Recent findings suggest an involvement of reactive oxygen species (ROS) in signal transduction pathways leading to NF-kappa B activation.

NF-kappa B


Input: The present study was based on reports that antioxidants which eliminate ROS should block the activation of NF-kappa B and subsequently HIV transcription, and thus antioxidants can be used as therapeutic agents for AIDS.

NF-kappa B


Input: Incubation of Jurkat T cells (1 x 10(6) cells/ml) with a natural thiol antioxidant, alpha-lipoic acid, prior to the stimulation of cells was found to inhibit NF-kappa B activation induced by tumor necrosis factor-alpha (25 ng/ml) or by phorbol 12-myristate 13-acetate (50 ng/ml).

Jurkat T cells

NF-kappa B

tumor necrosis factor-alpha


Input: The inhibitory action of alpha-lipoic acid was found to be very potent as only 4 mM was needed for a complete inhibition, whereas 20 mM was required for N-acetylcysteine.


Input: These results indicate that alpha-lipoic acid may be effective in AIDS therapeutics.


Input: Reticuloendotheliosis virus long terminal repeat elements are efficient promoters in cells of various species and tissue origin, including human lymphoid cells.

Reticuloendotheliosis virus long terminal repeat elements

promoters

human lymphoid cells


Input: Promiscuous transcriptional activity of the reticuloendotheliosis virus (REV) long terminal repeat (LTR) was detected in transient expression assays using LTR- chloramphenicol acetyltransferase -encoding gene chimeras, and cells of diverse species and tissue type; levels of expression from two different REV LTRs correlate with reports of pathogenicity of the respective viruses in vivo.

reticuloendotheliosis virus (REV) long terminal repeat

LTR

LTR-

-encoding gene chimeras

REV LTRs

chloramphenicol acetyltransferase


Input: REVs do not encode a transactivator targeted to the viral LTR, and cells infected with Marek's disease virus, a herpesvirus with an overlapping host range, do not express factors that preferentially enhance expression from REV or avian sarcoma/leukemia virus LTRs.

viral LTR

avian sarcoma/leukemia virus LTRs


Input: REV LTRs work efficiently in human lymphoid cells, and are viable alternatives to promoters commonly used for expression of cloned genes.

REV LTRs

promoters

cloned genes

human lymphoid cells


Input: They may also prove useful in the identification of new, ubiquitous cellular transcription factors.

ubiquitous cellular transcription factors


Input: A novel Ets-related transcription factor, Elf-1, binds to human immunodeficiency virus type 2 regulatory elements that are required for inducible trans activation in T cells.

Ets-related transcription factor

human immunodeficiency virus type 2 regulatory elements

T cells


Input: Human immunodeficiency virus type 1 (HIV-1) and HIV-2 are structurally related retroviruses which both cause AIDS in humans.


Input: Although both viruses establish latency in quiescent human-peripheral-blood T cells, the asymptomatic phase of HIV-2 infection may be more prolonged than that of HIV-1.

human-peripheral-blood T cells


Input: The latent phases of both HIV-1 and HIV-2 infection have been shown to be disrupted by T-cell activation, a process that requires host cell transcription factors.


Input: In the case of HIV-1, the transcription factor NF-kappa B is sufficient for inducible transcriptional activation.

NF-kappa B


Input: In contrast, factors in addition to NF-kappa B are required to activate HIV-2 transcription in infected T cells.

NF-kappa B

infected T cells


Input: In this report, we demonstrate that a novel Ets-related transcription factor, Elf-1, binds specifically to two purine-rich motifs in the HIV-2 enhancer.

Ets-related transcription factor

two purine-rich motifs

HIV-2 enhancer


Input: Mutagenesis experiments demonstrated that these Elf-1 binding sites are required for induction of HIV-2 transcription following T-cell-receptor-mediated T-cell activation.

Elf-1 binding sites


Input: Moreover, Elf-1 is the only factor present in activated T-cell nuclear extracts that binds to these sites in electrophoretic mobility shift assays.


Input: Thus, Elf-1 is a novel transcription factor that appears to be required for the T-cell-receptor-mediated trans activation of HIV-2 gene expression.

novel transcription factor


Input: These results may explain differences in the clinical spectra of diseases caused by HIV-1 and HIV-2 and may also have implications for the design of therapeutic approaches to HIV-2 infection.


Input: Okadaic acid is a potent inducer of AP-1, NF-kappa B, and tumor necrosis factor-alpha in human B lymphocytes.

NF-kappa B

tumor necrosis factor-alpha

human B lymphocytes


Input: Treatment of human B lymphocytes with an optimal concentration of okadaic acid, an inhibitor of phosphatases 1 and 2A, resulted in the induction of the transcription factor, AP-1 and a marked increase in NF-kappa B levels.

human B lymphocytes

transcription factor

NF-kappa B


Input: In contrast, no effect on the levels of the octamer binding proteins, Oct-1 or Oct-2, were found.

octamer binding proteins


Input: Since both AP-1 and NF-kappa B have been reported to be important in the induction of the tumor necrosis factor-alpha (TNF-alpha) gene we examined the effects of okadaic acid on TNF-alpha mRNA levels.

NF-kappa B

tumor necrosis factor-alpha

(TNF-alpha) gene

TNF-alpha mRNA


Input: Treatment with okadaic acid resulted in a striking increase in TNF-alpha mRNA transcripts within 1 h of stimulation and large amounts of TNF-alpha were released into the culture media.

TNF-alpha mRNA

TNF-alpha


Input: Although okadaic acid provides a potent inductive signal for AP-1 and NF-kappa B it did not induce either B cell proliferation or immunoglobulin secretion.

NF-kappa B

immunoglobulin


Input: Heterodimerization and transcriptional activation in vitro by NF-kappa B proteins.

NF-kappa B proteins


Input: The NF-kappa B family of transcription proteins represents multiple DNA binding, rel related polypeptides that contribute to regulation of genes involved in immune responsiveness and inflammation, as well as activation of the HIV long terminal repeat.

NF-kappa B family

transcription proteins

rel related polypeptides

HIV long terminal repeat


Input: In this study multiple NF-kappa B related polypeptides ranging from 85 to 45 kDa were examined for their capacity to interact with the PRDII regulatory element of interferon beta and were shown to possess distinct intrinsic DNA binding affinities for this NF-kappa B site and form multiple DNA binding homo- and hetero dimer complexes in co-renaturation experiments.

NF-kappa B related polypeptides

PRDII regulatory element

interferon beta

NF-kappa B site


Input: Furthermore, using DNA templates containing two copies of the PRDII domain linked to the rabbit beta globin gene, the purified polypeptides specifically stimulated NF-kappa B dependent transcription in an in vitro reconstitution assay as heterodimers but not as p50 homodimers.

DNA templates

PRDII domain

rabbit beta globin gene

NF-kappa B

p50 homodimers


Input: These experiments emphasize the role of NF-kappa B dimerization as a distinct level of transcriptional control that may permit functional diversification of a limited number of regulatory proteins.

NF-kappa B

regulatory proteins


Input: c-myc mRNA expression in minor salivary glands of patients with Sjogren's syndrome.

c-myc mRNA


Input: c-myc protooncogene is implicated in the pathogenesis of B cell lymphoid malignancies and high levels of c-myc mRNA expression are observed in activated blood mononuclear cells.

c-myc protooncogene

c-myc mRNA

activated blood mononuclear cells


Input: Sjogren's syndrome (SS) is characterized by lymphocytic infiltrates of exocrine glands, remarkable B cell hyperreactivity and a strong predisposition to B cell neoplasia.

lymphocytic infiltrates


Input: In this study, c-myc protooncogene mRNA expression in 29 labial minor salivary gland biopsies from patients with primary SS and 15 controls was examined using in situ hybridization histochemistry.

c-myc protooncogene

mRNA


Input: Two 40mer oligonucleotides from the 1st and the 2nd exon of the c-myc gene, labeled with 35S, were used as probes.

c-myc gene


Input: To detect the origin of the cell hybridized with a c-myc probe, a combined immunochemistry in situ hybridization histochemistry technique was used.

c-myc probe


Input: High c-myc mRNA expression was detected on acinar epithelial cells.

c-myc mRNA

acinar epithelial cells


Input: c-myc did not correlate with c-fos and c-jun protein expression.

c-myc

c-fos

c-jun


Input: Stronger c-myc mRNA expression was detected in labial salivary glands of patients with longer disease duration (p less than or equal to 0.002) and more intense T lymphocyte infiltrates (p less than 0.05) although these patients revealed no hypergammaglobulinemia.

c-myc mRNA

T lymphocyte infiltrates


Input: No correlation was observed between c-myc mRNA and B lymphocyte monoclonicity or lymphoma.

c-myc mRNA


Input: In conclusion, strong c-myc mRNA expression was observed on epithelial cells of labial salivary glands from patients with primary SS.

c-myc mRNA

epithelial cells


Input: Our findings may indicate the presence of a reactivated virus hosted in these cells.


Input: Corticosteroid receptors and lymphocyte subsets in mononuclear leukocytes in aging.

Corticosteroid receptors

lymphocyte subsets

mononuclear leukocytes


Input: Plasma cortisol and aldosterone levels and number of related receptors in mononuclear leukocytes were measured in 49 healthy aged subjects (62-97 yr) and in 21 adult controls (21-50 yr).

mononuclear leukocytes


Input: In all subjects, in addition, lymphocyte subsets were determined as an index of corticosteroid action.

lymphocyte subsets


Input: The mean number of type I and type II receptors was significantly lower in aged subjects than in controls (respectively, 198 +/- 96 and 272 +/- 97 receptors /cell for type I, and 1,794 +/- 803 and 3,339 +/- 918 for type II receptors ).

receptors

type I

II receptors


Input: Plasma aldosterone and cortisol and lymphocyte subsets were not different in the two groups.

lymphocyte subsets


Input: All of the parameters were also tested for correlation, and a significant inverse correlation was found between age and type I and type II receptors when all subjects were plotted and between aged and CD4 and age and CD4/CD8 in the aged group.

type I

type II receptors


Input: These data show that aged subjects have reductions of corticosteroid receptors that are not associated with increase of related steroids and that this situation probably represents a concomitant of the normal aging process.

corticosteroid receptors


Input: T cell-specific negative regulation of transcription of the human cytokine IL-4.

human cytokine IL-4


Input: IL-4 secreted by activated T cells is a pleiotropic cytokine affecting growth and differentiation of diverse cell types such as T cells, B cells, and mast cells.

pleiotropic cytokine

activated T cells

T cells

B cells

mast cells


Input: We investigated the upstream regulatory elements of the human IL-4 promoter.

upstream regulatory elements

human IL-4 promoter


Input: A novel T cell-specific negative regulatory element (NRE) composed of two protein-binding sites were mapped in the 5' flanking region of the IL-4 gene: -311CTCCCTTCT-303 (NRE-I) and -288CTTTTTGCTT-TGC-300 (NRE-II ).

novel T cell-specific negative regulatory element

NRE

IL-4 gene

NRE-I

NRE-II


Input: A T cell-specific protein Neg-1 and a ubiquitous protein Neg-2 binding to NRE-I and NRE-II, respectively, were identified.

T cell-specific protein

ubiquitous protein

NRE-I

NRE-II


Input: Furthermore, a positive regulatory element was found 45 bp downstream of the NRE.

positive regulatory element

45 bp downstream

NRE


Input: The enhancer activity of the PRE was completely suppressed when the NRE was present.

PRE

NRE


Input: These data suggest that IL-4 promoter activity is normally down-regulated by an NRE via repression of the enhancer positive regulatory element.

IL-4 promoter

NRE

enhancer positive regulatory element


Input: These data may have implications for the stringent control of IL-4 expression in T cells.

T cells


Input: Interleukin 6-induced differentiation of a human B cell line into IgM-secreting plasma cells is mediated by c-fos.

human B cell line

IgM-secreting plasma cells

c-fos


Input: The role of the protooncogene c-fos in interleukin (IL) 6 -induced B cell differentiation was assessed.

protooncogene c-fos

interleukin (IL) 6


Input: Treatment of SKW 6.4 cells with IL 6 induced a transient and early stimulation of c-fos sense mRNA expression.

IL 6

c-fos sense mRNA


Input: The effect appeared within 30 min and returned to basal levels after 2 h.


Input: The addition of antisense oligonucleotides to c-fos significantly inhibited IL 6 -induced IgM production by SKW 6.4 cells (p less than 0.001), whereas control oligonucleotides had no inhibitory effect.

c-fos

IL 6

IgM

SKW 6.4 cells


Input: These results indicate that activation of c-fos is involved in IL 6 -induced differentiation of SKW 6.4 cells into IgM-secreting cells.

c-fos

IL 6

SKW 6.4 cells

IgM-secreting cells


Input: Transcriptional regulation during T-cell development: the alpha TCR gene as a molecular model.

T-cell

alpha TCR gene


Input: The regulation of gene expression during lymphocyte differentiation is a complex process involving interactions between multiple positive and negative transcriptional regulatory elements.

lymphocyte


Input: In this article, transcriptional regulation of the archetypal T-cell -specific gene, alpha TCR, is discussed.

archetypal

-specific gene

alpha TCR

T-cell


Input: Major recent developments, including the identification of novel families of transcription factors that regulate multiple T-cell genes during thymocyte ontogeny and T-cell activation, are described.

transcription factors

genes

T-cell

T-cell


Input: Photoaffinity labeling of plasma membrane receptors for aldosterone from human mononuclear leukocytes.

plasma membrane receptors

human mononuclear leukocytes


Input: Non-genomic effects of aldosterone on the sodium-proton-antiport have been shown in human mononuclear leukocytes which could be related to a new aldosterone membrane receptor.

sodium-proton-antiport

aldosterone membrane receptor

human mononuclear leukocytes


Input: In the present paper plasma membranes from human mononuclear leukocytes were covalently photolabeled with a [125I]-aldosterone derivative.

human mononuclear leukocytes


Input: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed significant aldosterone binding at a molecular weight of approximately 50000 Dalton which was absent with 1 microM cold aldosterone, but not cortisol in the binding media.


Input: The presence of the sulfhydryl agent dithiothreitol did not affect results suggesting the absence of disulfide bridges in the steroid binding domain of the receptor.

disulfide bridges

steroid binding domain


Input: These data are the first to define the molecular weight of the membrane receptor for aldosterone.

membrane receptor


Input: Redox status of cells influences constitutive or induced NF-kappa B translocation and HIV long terminal repeat activity in human T and monocytic cell lines.

NF-kappa B

HIV long terminal repeat


Input: We have tested the hypothesis that cellular activation events occurring in T lymphocytes and monocytes and mediated through translocation of the transcription factor NF-kappa B are dependent upon the constitutive redox status of these cells.

T lymphocytes

monocytes

transcription factor

NF-kappa B


Input: We used phenolic, lipid-soluble, chain-breaking antioxidants (butylated hydroxyanisole (BHA ), nordihydroquairetic acid, or alpha-tocopherol (vitamin E) to show that peroxyl radical scavenging in unstimulated and PMA- or TNF- stimulated cells blocks the functions depending on NF-kappa B activation.

NF-kappa B


Input: BHA was found to suppress not only PMA- or TNF- induced, but also constitutive, HIV-enhancer activity concomitant to an inhibition of NF-kappa B binding activity in both lymphoblastoid T (J.Jhan) and monocytic (U937) cell lines.

NF-kappa B

lymphoblastoid T

J.Jhan

monocytic (

U937) cell lines


Input: This was also true for KBF (p50 homodimer) binding activity in U937 cells.

U937 cells


Input: Secretion of TNF, the product of another NF-kappa B -dependent gene, was abolished by BHA in PMA-stimulated U937 cells.

TNF

NF-kappa B

-dependent gene

PMA-stimulated U937 cells


Input: The anti-oxidative effect of BHA was accompanied by an increase in thiol, but not glutathione, content in stimulated and unstimulated T cell, whereas TNF stimulation itself barely modified the cellular thiol level.

stimulated and unstimulated T cell

TNF


Input: Oxidative stress obtained by the addition of H2O2 to the culture medium of J.Jhan or U937 cells could not by itself induce NF-kappa B activation.

J.Jhan

U937 cells

NF-kappa B


Input: These observations suggest that TNF and PMA do not lead to NF-kappa B activation through induction of changes in the cell redox status.

TNF

PMA

NF-kappa B


Input: Rather, TNF and PMA can exert their effect only if cells are in an appropriate redox status, because prior modification toward reduction with BHA treatment prevents this activation.

TNF

PMA


Input: It appears that a basal redox equilibrium tending toward oxidation is a prerequisite for full activation of transduction pathways regulating the activity of NF-kappa B -dependent genes.

NF-kappa B -dependent genes


Input: Selection of optimal kappa B/Rel DNA-binding motifs: interaction of both subunits of NF-kappa B with DNA is required for transcriptional activation.

kappa B/Rel DNA-binding motifs

NF-kappa B


Input: Analysis of the p50 and p65 subunits of the NF-kappa B transcription factor complex has revealed that both proteins can interact with related DNA sequences through either homo- or hetero dimer formation.

p65 subunits

NF-kappa B transcription factor complex

DNA sequences


Input: In addition, the product of the proto-oncogene c-rel can bind to similar DNA motifs by itself or as a heterodimer with p50 or p65.

proto-oncogene c-rel

DNA motifs


Input: However, these studies have used a limited number of known kappa B DNA motifs, and the question of the optimal DNA sequences preferred by each homodimer has not been addressed.

kappa B DNA motifs

optimal DNA sequences


Input: Using purified recombinant p50, p65, and c-Rel proteins, optimal DNA-binding motifs were selected from a pool of random oligonucleotides.

c-Rel proteins

optimal DNA-binding motifs


Input: Alignment of the selected sequences allowed us to predict a consensus sequence for binding of the individual homodimeric Rel-related proteins, and DNA-protein binding analysis of the selected DNA sequences revealed sequence specificity of the proteins.

homodimeric Rel-related proteins

selected DNA sequences


Input: Contrary to previous assumptions, we observed that p65 homodimers can interact with a subset of DNA sequences not recognized by p50 homodimers.

p50 homodimers

DNA sequences


Input: Differential binding affinities were also obtained with p50- and c-Rel- selected sequences.


Input: Using either a p50- or p65- selected kappa B motif, which displayed differential binding with respect to the other protein, little to no binding was observed with the heterodimeric NF-kappa B complex.

heterodimeric NF-kappa B complex


Input: Similarly, in transfection experiments in which the selective kappa B binding sites were used to drive the expression of a chloramphenicol acetyltransferase reporter construct, the p65 -and p50 -selected motifs were activated only in the presence of p65 and p50/65 (a chimeric protein with the p50 DNA binding domain and p65 activation domain) expression vectors, respectively, and neither demonstrated a significant response to stimuli that induce NF-kappa B activity.

selective kappa B binding sites

reporter construct

chloramphenicol acetyltransferase

chimeric protein

p50 DNA binding domain

p65 activation domain

NF-kappa B


Input: These findings demonstrate that interaction of both subunits of the heterodimeric NF-kappa B complex with DNA is required for DNA binding and transcriptional activation and suggest that transcriptional activation mediated by the individual rel-related proteins will differ dramatically, depending on the specific kappa B motifs present.

heterodimeric

NF-kappa B complex

rel-related proteins

specific kappa B motifs


Input: NF-kappa B -dependent induction of the NF-kappa B p50 subunit gene promoter underlies self-perpetuation of human immunodeficiency virus transcription in monocytic cells.

NF-kappa B

NF-kappa B

subunit gene promoter

monocytic cells


Input: The molecular mechanisms underlying the sustained nuclear translocation of NF-kappa B observed in U937 monocytic cells chronically infected with human immunodeficiency virus (HIV) were studied.

NF-kappa B

monocytic cells


Input: The activity of the promoter regulating the synthesis of the p105 precursor of the NF-kappa B p50 subunit was enhanced in these cells.

promoter

p105 precursor

NF-kappa B

p50 subunit


Input: Deletions in this promoter indicated that this upregulation was mediated through the NF-kappa B- but not the AP-1-binding motif, by bona fide p50/p65 heterodimers.

promoter

NF-kappa B-

AP-1-binding motif

p50/p65 heterodimers


Input: Analysis of cytosolic extracts indicated that NF-kappa B levels were increased in HIV -infected cells.

NF-kappa B

HIV -infected cells


Input: In contrast to the transient NF-kappa B activation induced by phorbol ester, the permanent NF-kappa B translocation induced by HIV infection was not dependent on PKC isoenzymes alpha and beta as shown by the use of a specific inhibitor (GF 109203X ).

NF-kappa B

NF-kappa B

PKC isoenzymes


Input: These observations indicate that during chronic HIV infection of U937 cells, continuous NF-kappa B (p50/p65) translocation results in p105 promoter upregulation with subsequent cytosolic NF-kappa B accumulation, ready for further translocation.

U937 cells

NF-kappa B

NF-kappa B

p105 promoter


Input: This HIV -mediated mechanism results in a self-perpetuating loop of NF-kappa B production.

NF-kappa B


Input: Activation of NF-kappa B by interleukin 2 in human blood monocytes.

NF-kappa B

interleukin 2

human blood

monocytes


Input: We report here that interleukin 2 (IL-2) acts on human blood monocytes by enhancing binding activity of the transcription factor NF-kappa B to its consensus sequence in the 5' regulatory enhancer region of the IL-2 receptor alpha chain (p55 ).

interleukin 2

transcription factor NF-kappa B

human blood

monocytes

5' regulatory enhancer region

receptor alpha chain


Input: Similarly, IL-2 activates NF-kappa B in the human monocytic cell line U 937, but not in resting human T-cells.

NF-kappa B

human monocytic cell line U 937

resting human T-cells


Input: This effect is detectable within 15 min and peaks 1 h after exposure to IL-2.


Input: Enhanced NF-kappa B binding activity is followed by functional activation in that inducibility of the IL-2 receptor alpha chain is mediated by enhanced NF-kappa B binding and that a heterologous promoter containing the NF-kappa B consensus sequence (-291 to -245) of the IL-2 receptor alpha chain gene is activated.

NF-kappa B

IL-2 receptor alpha chain

NF-kappa B

NF-kappa B consensus sequence

-291 to -245

IL-2 receptor alpha chain gene


Input: In addition, IL-2 is capable of increasing transcript levels of the p50 gene coding for the p50 subunit of the NF-kappa B transcription factor, whereas mRNA levels of the p65 NF-kappa B gene remained unchanged.

p50 subunit

NF-kappa B

NF-kappa B

gene


Input: Studies on the biological activity of triiodothyronine sulfate.


Input: Hepatic microsomes and isolated hepatocytes in short term culture desulfate T3 sulfate (T3SO4 ).

Hepatic microsomes

isolated hepatocytes


Input: We, therefore, wished to determine whether T3SO4 could mimic the action of thyroid hormone in vitro.


Input: T3SO4 had no thyromimetic effect on the activity of Ca(2+)-ATPase in human erythrocyte membranes at doses up to 10,000 times the maximally effective dose of T3 (10(-10) mol/L).


Input: In GH4C1 pituitary cells, T3SO4 failed to displace [125I]T3 from nuclear receptors in intact cells or soluble preparations.

GH4C1 pituitary cells

intact cells

nuclear receptors


Input: Thus, T3SO4 was not directly thyromimetic in either an isolated human membrane system or a pituitary cell system in which nuclear receptor occupancy correlates with GH synthesis.


Input: Thyroid hormones inhibit [3H]glycosaminoglycan synthesis by cultured human dermal fibroblasts, and T3SO4 displayed about 0.5% the activity of T3 at 72 h.

cultured human dermal fibroblasts


Input: Human fibroblasts contained roughly the same level of microsomal p-nitrophenyl sulfatase activity as that previously observed in hepatic microsomes.

Human fibroblasts

hepatic microsomes

p-nitrophenyl sulfatase


Input: Propylthiouracil (50 mumol/L) did not affect the action of T3SO4, suggesting that deiodination was not important for this activity of T3SO4.


Input: Thus, it appears T3SO4 has no intrinsic biological activity, but, under certain circumstances, may be reactivated by desulfation.


Input: Human T cell activation through the activation-inducer molecule/CD69 enhances the activity of transcription factor AP-1.

activation-inducer molecule/CD69

transcription factor AP-1


Input: The induction of the AP-1 transcription factor has been ascribed to the early events leading to T cell differentiation and activation.

AP-1 transcription factor


Input: We have studied the regulation of AP-1 activity in human peripheral blood T lymphocytes stimulated through the activation inducer molecule (AIM)/ CD69 activation pathway.

human peripheral blood T lymphocytes


Input: Phorbol esters are required to induce AIM/CD69 cell-surface expression as well as for triggering the proliferation of T cells in conjunction with anti-AIM mAb.

anti-AIM mAb

T cells


Input: Mobility shift assays showed that addition of anti-AIM mAb to PMA -treated T lymphocytes markedly enhanced the binding activity of AP-1 to its cognate sequence, the phorbol ester response element.

anti-AIM mAb

PMA

-treated T lymphocytes

phorbol ester response element


Input: In contrast, anti-AIM mAb did not induce any change in the binding activity of NF-kappa B, a transcription factor whose activity is also regulated by protein kinase C.

anti-AIM mAb

NF-kappa B

transcription factor

protein kinase C


Input: The increase in AP-1 -binding activity was accompanied by the marked stimulation of the transcription of c-fos but not that of c-jun.

c-fos

c-jun


Input: Blockade of the DNA-binding complexes with an anti-Fos mAb demonstrated a direct participation of c-Fos in the AP-1 complexes induced by anti-AIM mAb.

DNA-binding complexes

anti-Fos mAb

c-Fos

AP-1 complexes

anti-AIM mAb


Input: Most of the AP-1 activity could be eliminated when the anti-AIM mAb was added to the culture medium in the presence of cycloheximide, suggesting that de novo protein synthesis is crucial for the induction of AP-1 -binding activity.

anti-AIM mAb


Input: These data provide the evidence that activation of human peripheral blood T cells through the AIM activation pathway regulate the activity of AP-1.

human peripheral blood T cells


Input: Therefore, this pathway appears as a crucial step in the initiation of early T cell activation events.


Input: Gangliosides suppress tumor necrosis factor production in human monocytes.

tumor necrosis factor

human

monocytes


Input: Both normal and malignant cells contain gangliosides as important cell membrane constituents that, after being shed, may influence cells of the immune system.


Input: We have studied the impact of gangliosides on the expression of TNF in blood monocytes and in the monocytic cell line Mono Mac 6.

TNF

blood monocytes

monocytic cell line Mono Mac 6


Input: Although under standard culture conditions, bovine brain gangliosides (100 micrograms/ml) suppressed LPS-stimulated TNF production 5-fold in PBMC and 10-fold in Mono Mac 6 cells, suppression was more efficient under serum-free conditions.

TNF

PBMC

Mono Mac 6 cells


Input: Looking at highly purified gangliosides, GD3, GD1a, GM3, GM2, and GM1 were all effective in reducing TNF production in PBMC, and in Mono Mac 6 by factor 10 to 50.

TNF

PBMC

Mono Mac 6


Input: The suppressive activity was lost in molecules, lacking the sugar moiety or the lipid moiety.


Input: Gangliosides appear to act at an early step of activation in that TNF transcripts were reduced and the mobilization of the nuclear factor kappa B was blocked.

TNF

nuclear factor kappa B

transcripts


Input: Furthermore, in time kinetics, gangliosides were effective for up to 30 min after addition of LPS, but not thereafter.


Input: However, the expression of the CD14 Ag, a receptor molecule for LPS-LPS binding protein complexes, was unaffected by gangliosides.

CD14 Ag

receptor molecule

LPS-LPS binding protein complexes


Input: Finally, when using Staphylococcus aureus or platelet activating factor as a stimulus, gangliosides were able to suppress TNF production in Mono Mac 6 cells by factor 5 to 10, as well.

platelet activating factor

TNF

Mono Mac 6 cells


Input: On the other hand, phorbol ester -induced production of O2- was similar in cells treated with and without gangliosides.


Input: Taken together, our data demonstrate that TNF gene expression in monocytes induced by different types of stimuli can be blocked by gangliosides at an early step of signal transduction.

TNF

monocytes


Input: A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site.

mitogen-inducible gene product

p50/p105-NF-kappa B

kappa B site


Input: A Rel-related, mitogen-inducible, kappa B-binding protein has been cloned as an immediate-early activation gene of human peripheral blood T cells.

Rel-related, mitogen-inducible, kappa B-binding protein

immediate-early activation gene

human peripheral blood T cells


Input: The cDNA has an open reading frame of 900 amino acids capable of encoding a 97-kDa protein.

cDNA

open reading frame

900 amino acids

97-kDa protein


Input: This protein is most similar to the 105-kDa precursor polypeptide of p50-NF-kappa B.

p50-NF-kappa B


Input: Like the 105-kDa precursor, it contains an amino-terminal Rel-related domain of about 300 amino acids and a carboxy-terminal domain containing six full cell cycle or ankyrin repeats.

amino-terminal Rel-related domain

carboxy-terminal domain

full cell cycle

ankyrin repeats


Input: In vitro-translated proteins, truncated downstream of the Rel domain and excluding the repeats, bind kappa B sites.

vitro-translated proteins

Rel domain

kappa B sites


Input: We refer to the kappa B-binding, truncated protein as p50B by analogy with p50-NF-kappa B and to the full-length protein as p97.

kappa B-binding, truncated protein

p50-NF-kappa B


Input: p50B is able to form heteromeric kappa B-binding complexes with RelB, as well as with p65 and p50, the two subunits of NF-kappa B.

heteromeric kappa B-binding complexes

RelB

NF-kappa B


Input: Transient-transfection experiments in embryonal carcinoma cells demonstrate a functional cooperation between p50B and RelB or p65 in transactivation of a reporter plasmid dependent on a kappa B site.

embryonal carcinoma cells

RelB

reporter plasmid

kappa B site


Input: The data imply the existence of a complex family of NF-kappa B -like transcription factors.

NF-kappa B -like transcription factors


Input: Surrogate thyroglobulin receptors and T cell proliferation in Hashimoto's thyroiditis.

thyroglobulin receptors


Input: Immunoglobulin molecules on the surface of a B lymphocyte are the endogenous "receptors" to which specific antigens bind.

Immunoglobulin molecules

B lymphocyte


Input: Studies in mice have shown that a monoclonal antibody, conjugated with palmitate to provide a lipid tail, can be inserted into the cell membrane to provide a " surrogate" antigen receptor.

monoclonal antibody

surrogate" antigen receptor


Input: We have investigated whether a palmitate conjugate of a human monoclonal antibody specific for thyroglobulin (TG) could function as a surrogate TG receptor on blood mononuclear cells separated into fractions enriched for T cells or depleted of T cells (non-T cells ).

palmitate conjugate

human

monoclonal antibody

thyroglobulin

TG

surrogate

TG receptor

blood mononuclear cells

T cells

T cells

non-T cells


Input: Using flow cytometry, we detected surrogate TG receptors on non-T (but not on T) cells from 11 of 11 individuals studied (5 Hashimoto patients and 6 control donors ).

surrogate TG receptors

non-T (but not on T) cells


Input: In contrast, endogenous TG receptors could only be detected on non- T cells from 1 of 3 Hashimoto patients and from 0 of 4 control donors.

endogenous TG receptors

non- T cells


Input: Because of the efficient binding of TG by surrogate receptors on non-T cells, we assessed the ability of such cells to present TG to T cells.

TG

surrogate receptors

TG

non-T cells

T cells


Input: Proliferation in response to TG was observed in T cells from only 1 of 5 Hashimoto patients.

TG

T cells


Input: This low frequency of response was no different from that previously detected using cultures of T cells and autologous dendritic cells.

T cells

autologous dendritic cells


Input: Therefore, the successful generation of surrogate receptors on non-T cells is not associated with more efficient TG presentation of T cells.

surrogate receptors

TG

non-T cells

T cells


Input: Furthermore, the significance of the present study is that the T cells, not the antigen-presenting cells, are likely to be the limiting element in the T cell proliferative response to TG and other thyroid autoantigens.

T cells

antigen-presenting cells

TG

thyroid autoantigens


Input: Targeted degradation of c-Fos, but not v-Fos, by a phosphorylation-dependent signal on c-Jun.

c-Fos

v-Fos

phosphorylation-dependent signal

c-Jun


Input: The proto-oncogene products c-Fos and c-Jun heterodimerize through their leucine zippers to form the AP-1 transcription factor.

proto-oncogene products

c-Fos

c-Jun

leucine zippers

AP-1 transcription factor


Input: The transcriptional activity of the heterodimer is regulated by signal-dependent phosphorylation and dephosphorylation events.


Input: The stability of c-Fos was found to also be controlled by intracellular signal transduction.

c-Fos


Input: In transient expression and in vitro degradation experiments, the stability of c-Fos was decreased when the protein was dimerized with phosphorylated c-Jun.

c-Fos

phosphorylated c-Jun


Input: c-Jun protein isolated from phorbol ester-induced cells did not target c-Fos for degradation, which suggests that c-Fos is transiently stabilized after stimulation of cell growth.

c-Jun

c-Fos

c-Fos

phorbol ester-induced cells


Input: v-Fos protein, the retroviral counterpart of c-Fos, was not susceptible to degradation targeted by c-Jun.

v-Fos protein

c-Fos

c-Jun


Input: The regulation of the human tumor necrosis factor alpha promoter region in macrophage, T cell, and B cell lines.

human tumor necrosis factor alpha promoter region

macrophage

T cell

B cell lines


Input: The 1311-base pair human tumor necrosis factor (TNF) alpha promoter region was fused to the luciferase (Luc) reporter gene and studied in a transient transfection system in three TNF producing cell lines, the U937 macrophage cell line, the MLA 144 T cell line, and the 729-6 B cell line.

1311-base pair human tumor necrosis factor (TNF) alpha promoter region

luciferase (Luc) reporter gene

TNF producing cell lines

U937 macrophage cell line

MLA 144 T cell line

729-6 B cell line


Input: This full length promoter construct can be induced by phorbol 13-myristate acetate (PMA) in each of these cell types.


Input: Analysis of a series of 5'-truncations showed several peaks of basal and PMA induced activity suggesting the presence of several positive and negative regulatory elements.

positive

negative regulatory elements


Input: A PMA responsive element was localized to a region between -95 and -36 bp relative to the transcription start site.

PMA responsive element

-95 and -36 bp

transcription start site


Input: Within this region, single AP-2- and AP-1- like consensus sequences were noted.


Input: These AP-2 and AP-1 sites were each modified with a double point mutation.

AP-1 sites


Input: A modest (20-50%) reduction in TNF promoter activity was observed with the AP-2 site mutation.

TNF promoter

AP-2 site mutation


Input: However, mutation of the AP-1 site markedly diminished both the basal and PMA-activated promoter activity.

AP-1 site


Input: Also co-transfections of the wild-type promoter construct with an AP-1/c-jun expression vector resulted in augmented basal and PMA -induced promoter activity.

wild-type promoter construct

AP-1/c-jun expression vector


Input: Stable expression of transdominant Rev protein in human T cells inhibits human immunodeficiency virus replication.

transdominant Rev protein

human T cells


Input: The human immunodeficiency virus (HIV) Rev protein is essential for viral structural protein expression (Gag, Pol, and Env) and, hence, for viral replication.

Rev protein

Gag

Pol

Env


Input: In transient transfection assays, mutant forms of Rev have been identified that inhibit wild-type Rev activity and therefore suppress viral replication.

Rev

Rev


Input: To determine whether such transdominant Rev proteins could provide long-term protection against HIV infection without affecting T cell function, T leukemia cell lines were stably transduced with a retroviral vector encoding a transdominant mutant of the Rev protein, M10.

transdominant Rev proteins

Rev protein

T leukemia cell lines

retroviral vector


Input: While all the M10 -expressing cell lines remained infectable by HIV-1, these same cells failed to support a productive replication cycle when infected with a cloned isolate of HIV-1.

M10 -expressing cell lines


Input: In addition, two out of three M10 -expressing CEM clones were also resistant to highly productive infection by a heterogeneous HIV-1 pool.

M10 -expressing CEM clones


Input: Expression of M10 did not affect induction of HIV transcription mediated by the kappa B regulatory element or Tat.

Tat

kappa B regulatory element


Input: Importantly, constitutive expression of Rev M10 did not alter the secretion of interleukin 2 in response to mitogen stimulation of EL-4 and Jurkat cells.

Rev M10

interleukin 2

Jurkat cells


Input: The inhibition of HIV infection in cells stably expressing a transdominant Rev protein, in the absence of any deleterious effect on T cell function, suggests that such a strategy could provide a therapeutic effect in the T lymphocytes of acquired immunodeficiency syndrome patients.

transdominant Rev protein

T lymphocytes


Input: Simple derivation of TFIID-dependent RNA polymerase II transcription systems from Schizosaccharomyces pombe and other organisms, and factors required for transcriptional activation.

RNA polymerase II


Input: Resolution of whole cell extract through two chromatographic steps yields a single protein fraction requiring only the addition of TFIID for the initiation of transcription at RNA polymerase II promoters.

TFIID

RNA polymerase II

promoters


Input: This approach allows the convenient generation of RNA polymerase II transcription systems from Saccharomyces cerevisiae, human lymphocytes, and Schizosaccharomyces pombe.

RNA polymerase II

human lymphocytes


Input: TFIIDs from all three organisms are interchangeable among all three systems.

TFIIDs


Input: The S. cerevisiae and Sch. pombe systems support effects of acidic activator proteins, provided a further protein fraction from S. cerevisiae is supplied.

acidic activator proteins


Input: This further fraction is distinct from the mediator of transcriptional activation described previously and represents a second component in addition to general initiation factors that may facilitate a response to acidic activators.

general initiation factors

acidic activators


Input: Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid.

c-jun


Input: The present work has examined the effects of okadaic acid, an inhibitor of type 1 and 2A protein phosphatases, on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells.

c-jun

U-937 leukemia cells


Input: The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by: (a) growth arrest; (b) increases in Mac-1 cell surface antigen expression; (c) down-regulation of c-myc transcripts; and (d) induction of tumor necrosis factor gene expression.

Mac-1 cell surface antigen

c-myc transcripts

tumor necrosis factor gene


Input: This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels, which were maximal at 6 h.

c-jun mRNA


Input: Similar effects were obtained for the c-fos gene.

c-fos gene


Input: Run-on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure.

c-jun

U-937 cells


Input: c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide, whereas inhibition of protein synthesis had little, if any, effect on okadaic acid -induced c-jun transcription.

c-jun mRNA

c-jun


Input: The half-life of c-jun mRNA was similar (45-50 min) in both untreated and okadaic acid -induced cells.

c-jun mRNA

okadaic acid -induced cells


Input: In contrast, treatment with both okadaic acid and cycloheximide was associated with stabilization (t 1/2 = 90 min) of c-jun transcripts.

c-jun transcripts


Input: Taken together, these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism.

c-jun


Input: Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1, we also studied transcription of c-jun promoter (positions -132/+170)-reporter gene constructs with and without a mutated AP-1 element.

c-jun gene

c-jun promoter (positions -132/+170)-reporter gene constructs

AP-1 element


Input: (ABSTRACT TRUNCATED AT 250 WORDS)


Input: Mitogen stimulation of T-cells increases c-Fos and c-Jun protein levels, AP-1 binding and AP-1 transcriptional activity.

c-Fos

c-Jun


Input: We have analysed the effect of mitogenic lectins on c-Fos and c-Jun protein levels as well as on activator protein-1 (AP-1) binding and enhancer activity in Jurkat T-cells.

c-Fos

c-Jun


Input: Both c-Fos and c-Jun protein levels were increased after Con A and PHA stimulation.

c-Fos

c-Jun


Input: Since T-cell stimulation increases both intracellular Ca2+ and cAMP levels and activates protein kinase C (PKC), the possible involvement of these intracellular messengers in c-Fos and c-Jun induction was tested.

c-Fos

c-Jun


Input: PMA, which directly activates PKC, mimicked the effect of the lectins on c-Fos and c-Jun, but elevation of either intracellular Ca2+ or cAMP levels had little or no effect.

c-Jun


Input: The mitogen-induced increase of c-Fos and c-Jun immunoreactivity was inhibited by H-7, a kinase inhibitor with relatively high specificity for PKC, and less efficiently by H-8, a structurally related kinase inhibitor less active on PKC, but more active on cyclic nucleotide-dependent kinases.

c-Fos

c-Jun


Input: Con A stimulation was found to increase both binding of AP-1 to the AP-1 consensus sequence, TRE, and AP-1 enhancer activity, in Jurkat cells.

Jurkat cells


Input: PMA was also found to increase the AP-1 enhancer activity, whereas elevation of Ca2+ or cAMP had only minor effects.


Input: We conclude that stimulation with mitogenic lectins is sufficient to increase both c-Fos and c-Jun protein levels, AP-1 binding and AP-1 enhancer activity in Jurkat cells and that they act via mechanisms that could involve the activation of PKC.

c-Fos

c-Jun

Jurkat cells


Input: An 11-base-pair DNA sequence motif apparently unique to the human interleukin 4 gene confers responsiveness to T-cell activation signals.

11-base-pair DNA sequence motif

human interleukin 4 gene


Input: We have identified a DNA segment that confers responsiveness to antigen stimulation signals on the human interleukin (IL) 4 gene in Jurkat cells.

DNA segment

human interleukin (IL) 4 gene

Jurkat cells


Input: The human IL-4 gene, of 10 kilobases, is composed of four exons and three introns.

human IL-4 gene

exons

introns


Input: A cis-acting element (P sequence) resides in the 5' upstream region; no additional DNA segments with enhancer activity were identified in the human IL-4 gene.

cis-acting element

P sequence

5' upstream region

DNA segments

human IL-4 gene


Input: For further mapping purposes, a fusion promoter was constructed with the granulocyte/macrophage colony-stimulating factor basic promoter containing 60 base pairs of sequence upstream from the cap site of the mouse granulocyte/macrophage colony-stimulating factor gene and various lengths of the 5' upstream sequence of the IL-4 gene.

fusion promoter

granulocyte/macrophage colony-stimulating factor basic promoter

60 base pairs of sequence

cap site

gene

5' upstream sequence

IL-4 gene

mouse granulocyte/macrophage colony-stimulating factor


Input: The P sequence was located between positions -79 and -69 relative to the transcription start site of the human IL-4 gene, and this location was confirmed by base-substitution mutations.

P sequence

transcription start site

human

IL-4 gene


Input: The plasmids carrying multiple copies of the P sequence showed higher responsiveness to the stimulation.

P sequence


Input: The binding protein (s) that recognize the P sequence of the IL-4 gene were identified by DNA-mobility-shift assays.

binding protein

P sequence

IL-4 gene


Input: The binding of NF(P) (a DNA binding protein that specifically recognizes the P sequence) to the P sequence was abolished when oligonucleotides carrying base substitutions were used, indicating that the NF(P) interaction is sequence-specific and that binding specificity of the protein paralleled the sequence requirements for IL-4 expression in vivo.

NF(P)

DNA binding protein

NF(P)

P sequence

P sequence


Input: The P sequence does not share homology with the 5' upstream sequence of the IL-2 gene, even though surrounding sequences of the IL-4 gene share high homology with the IL-2 gene.

P sequence

5' upstream sequence

IL-2 gene

IL-4 gene

IL-2 gene


Input: We conclude that a different set of proteins recognize IL-2 and IL-4 genes.

proteins


Input: Leukotriene B4 stimulates c-fos and c-jun gene transcription and AP-1 binding activity in human monocytes.

human monocytes


Input: We have examined the effect of leukotriene B4 (LTB4 ), a potent lipid proinflammatory mediator, on the expression of the proto-oncogenes c-jun and c-fos.

proinflammatory mediator


Input: In addition, we looked at the modulation of nuclear factors binding specifically to the AP-1 element after LTB4 stimulation.

nuclear factors

AP-1 element


Input: LTB4 increased the expression of the c-fos gene in a time- and concentration-dependent manner.

c-fos gene


Input: The c-jun mRNA, which is constitutively expressed in human peripheral-blood monocytes at relatively high levels, was also slightly augmented by LTB4, although to a much lower extent than c-fos.

c-jun mRNA

human peripheral-blood monocytes

c-fos


Input: The kinetics of expression of the two genes were also slightly different, with c-fos mRNA reaching a peak at 15 min after stimulation and c-jun at 30 min.

c-fos mRNA

c-jun


Input: Both messages rapidly declined thereafter.


Input: Stability of the c-fos and c-jun mRNA was not affected by LTB4, as assessed after actinomycin D treatment.

c-fos

c-jun mRNA


Input: Nuclear transcription studies in vitro showed that LTB4 increased the transcription of the c-fos gene 7-fold and the c-jun gene 1.4-fold.

c-fos gene

c-jun gene


Input: Resting monocytes contained nuclear factors binding to the AP-1 element, but stimulation of monocytes with LTB4 induced greater AP-1 -binding activity of nuclear proteins.

Resting monocytes

monocytes

nuclear factors

nuclear proteins

AP-1 element


Input: These results indicate that LTB4 may regulate the production of different cytokines by modulating the yield and/or the function of transcription factors such as AP-1 -binding proto-oncogene products.

cytokines

transcription factors

proto-oncogene products


Input: Modulation of normal erythroid differentiation by the endogenous thyroid hormone and retinoic acid receptors: a possible target for v-erbA oncogene action.

retinoic acid receptors

v-erbA oncogene


Input: The v-erbA oncogene, a mutated version of the thyroid hormone receptor alpha (c-erbA/TR-alpha ), inhibits erythroid differentiation and constitutively represses transcription of certain erythrocyte genes, suggesting a normal function of the proto-oncogene c-erbA in erythropoiesis.

v-erbA oncogene

erythrocyte genes

proto-oncogene c-erbA

thyroid hormone receptor alpha

c-erbA/TR-alpha


Input: Here we demonstrate that the endogenous thyroid hormone receptor alpha (c-erbA/TR-alpha) and the closely related retinoic acid receptor alpha (RAR-alpha) play a role in the regulation of normal erythroid differentiation.

thyroid hormone receptor alpha

c-erbA/TR-alpha

retinoic acid receptor alpha

RAR-alpha


Input: Retinoic acid (RA) distinctly modulated the erythroid differentiation program of normal erythroid progenitors and erythroblasts reversibly transformed by a conditional tyrosine kinase oncogene.

normal erythroid progenitors

tyrosine kinase oncogene


Input: When added pulsewise to immature cells, differentiation was accelerated while more mature cells underwent premature cell death.

immature cells

mature cells


Input: Thyroid hormone (T3) alone caused similar but weaker effects.


Input: Interestingly, T3 strongly enhanced the action of RA, suggesting cooperative action of the two receptors in modulating erythroid differentiation.


Input: Expression of the human RAR-alpha in receptor-negative erythroblasts conferred RA -induced regulation of differentiation to the otherwise unresponsive cells, thus showing that the RAR-alpha is essential for the RA effect.

human

RAR-alpha

RAR-alpha

receptor-negative erythroblasts

unresponsive cells


Input: Likewise, enhanced expression of exogenous c-erbA/TR-alpha in erythroblasts rendered them susceptible to modulation of differentiation by T3, suggesting a similar function of both receptors.

exogenous c-erbA/TR-alpha

erythroblasts


Input: Activation of lymphokine genes in T cells: role of cis-acting DNA elements that respond to T cell activation signals.

lymphokine genes

cis-acting DNA elements

T cells


Input: Activation of T cells is initiated by the recognition of antigen on antigen presenting cells to exert the effector functions in immune and inflammatory responses.

T cells

antigen presenting cells

antigen


Input: Two types of helper T cell (Th) clones (Th1 and Th2) are defined on the basis of different patterns of cytokine (lymphokine) secretion.

helper T cell (Th) clones

cytokine

lymphokine


Input: They determine the outcome of an antigenic response toward humoral or cell-mediated immunity.


Input: Although lymphokine genes are coordinately regulated upon antigen stimulation, they are regulated by the mechanisms common to all as well as those which are unique to each gene.

lymphokine

genes


Input: For most lymphokine genes, a combination of phorbol esters (phorbol 12-myristate 13 acetate, PMA) and calcium ionophores (A23187) is required for their maximal induction.

lymphokine genes


Input: Yet phorbol ester alone or calcium ionophore alone produce several lymphokines.

lymphokines


Input: The production of the granulocyte-macrophage colony stimulating factor (GM-CSF) is completely dependent on the two signals.

granulocyte-macrophage colony stimulating factor

GM-CSF


Input: We have previously found a cis-acting region spanning the GM-CSF promoter region (positions -95 to +27) that confers inducibility to reporter genes in transient transfection assays.

cis-acting region

GM-CSF promoter region

reporter genes


Input: Further analysis identified three elements required for efficient induction, referred to as GM2, GC-box and conserved lymphokine element (CLE0 ).

GC-box

conserved

element

lymphokine


Input: GM2 defines a binding site for protein(s) whose binding is inducible by PMA.

binding site


Input: One protein, NF-GM2 is similar to the transcription factor NF-kB.

transcription factor

NF-kB


Input: GC-box is a binding site for constitutively bound proteins.

GC-box

binding site

constitutively bound proteins


Input: CLEO defines a binding site for protein(s) whose optimum binding is stimulated by PMA and A23187.

binding site


Input: Viral trans-activators such as Tax (human T cell leukemia virus-1, HTLV-1) and E2 (bovine papilloma virus, BPV) proteins are other agents which activate lymphokine gene expression by bypassing T cell receptor (TCR) mediated signaling.

Viral trans-activators

Tax

T cell receptor

TCR

lymphokine gene


Input: The trans-activation domain of E2 and Tax is interchangeable although they have no obvious sequence homology between them.

Tax


Input: The viral trans-activators appear to target specific DNA binding protein such as NF-kB and Sp1 to cis-acting DNA site and promote lymphokine gene expression without TCR -mediated stimulation.

viral trans-activators

DNA binding protein

NF-kB

TCR

cis-acting DNA site

lymphokine gene


Input: Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency.

Pit-1 gene


Input: Pit-1 is a pituitary-specific transcription factor that binds to and transactivates promoters of growth hormone and prolactin genes.

pituitary-specific transcription factor

promoters


Input: In three unrelated Japanese children with combined pituitary hormone deficiency, we identified three point mutations in the Pit-1 gene, Pro24Leu, Arg143Gln, and Arg271Trp, located on the major transactivation region, POU-specific domain, and POU-homeodomain, respectively.

gene

major transactivation region

POU-specific domain

POU-homeodomain


Input: Activation of protein kinase C and elevation of cAMP interact synergistically to raise c-Fos and AP-1 activity in Jurkat cells.

protein kinase C

c-Fos


Input: We have earlier found that in Jurkat cells activation of protein kinase C (PKC) enhances the cyclic adenosine monophosphate (cAMP) accumulation induced by adenosine receptor stimulation or activation of Gs.

protein kinase C

PKC

Gs


Input: Here we have therefore examined the effect of the phorbol ester PMA (phorbol 12-myristate 13-acetate) which stimulates PKC and a combination of the adenosine receptor agonist NECA (5'-(N-ethyl)-carboxamido adenosine) and forskolin to raise cAMP, on the levels of c-Fos and Jun and on the binding and transcriptional activity of the transcription factor, activator protein-1 (AP-1 ).

PKC

adenosine receptor

c-Fos

Jun

transcription factor

activator protein-1


Input: PMA treatment caused a concentration- and time-dependent increase in both c-Fos and Jun immunoreactivity in contrast to cAMP elevation that had only a slight effect.


Input: Both PMA and the combination of NECA and forskolin acted together either to increase (c-Fos) or decrease (Jun) protein levels as well as increasing AP-1 binding, as judged by gel-shift assay, and AP-1 transcriptional activity.

c-Fos

Jun


Input: Furthermore there was a clear-cut synergy between the PKC stimulator and the cAMP elevating agents.

PKC


Input: The results demonstrate that the simultaneous activation of PKC and elevation of cAMP leads to an enhanced AP-1 transcriptional activity in a T-leukemia cell line, suggesting that the previously observed interaction between the parallel signal transduction pathways may have functional consequences at the level of gene transcription.

PKC

T-leukemia cell line


Input: Inhibition of anti-CD3 monoclonal antibody -induced T-cell proliferation by dexamethasone, isoproterenol, or prostaglandin E2 either alone or in combination.

anti-CD3 monoclonal antibody


Input: The purpose of these studies was to investigate the modulation of the proliferation of human T cells obtained from peripheral blood by dexamethasone (DEX ), isoproterenol (ISO ), and prostaglandin E2 (PGE2 ).

human T cells


Input: The former two substances interact with T cells via the glucocorticoid and beta-adrenergic receptors respectively.

T cells


Input: When occupied by their natural ligands, glucocorticosteroids and catecholamines, these receptors have a role in modulating T-cell function during stress.


Input: During the inflammatory response increased levels of PGE2 bind to their receptors on T cells and thus alter responsiveness.

T cells


Input: Proliferation of T cells was induced by immobilized anti-CD3 monoclonal antibody (mAb) in the presence or absence of an additional costimulatory signal delivered by anti-CD28 mAb.

T cells

anti-CD3 monoclonal antibody

mAb

anti-CD28 mAb


Input: Various physiologic concentrations of DEX, ISO, or PGE2 were added at the time of initiation of the cultures and subsequent proliferation of the unstimulated T cells was determined.

T cells


Input: The results demonstrate that physiologic concentrations of all three of these agents inhibit the anti-CD3 mAb -induced proliferation of T cells.

anti-CD3 mAb

T cells


Input: Although DEX and PGE2 were equipotent in suppressing T-cell proliferation, ISO was much less effective.


Input: Because concomitant elevations in the peripheral levels of these substances may occur, experiments were performed to determine the T-cell inhibitory effects of DEX together with either PGE2 or ISO.


Input: Synergistic suppression of T-cell proliferation was observed when various concentrations of DEX and PGE2, but not DEX and ISO, were added to cultures.


Input: This synergistic suppression could not be explained by an increase in cAMP accumulation in T cells stimulated with DEX and PGE2.

T cells


Input: Finally, the addition of anti-CD28 mAb to anti-CD3 mAb-stimulated T cells overcame much of the suppression of proliferation induced by PGE2 or ISO but less so than that induced by DEX.

anti-CD28 mAb

anti-CD3 mAb-stimulated T cells


Input: In vivo footprint analysis of the HLA-DRA gene promoter: cell-specific interaction at the octamer site and up-regulation of X box binding by interferon gamma.

HLA-DRA gene promoter

octamer site

interferon gamma


Input: Analysis of the major histocompatibility complex class II gene promoter DRA has previously identified at least five cis-acting regions required for maximal expression.

major histocompatibility complex class II

gene promoter

DRA

cis-acting regions


Input: We have examined the DRA promoter for protein-DNA interactions in the intact cell, which may mediate transcriptional activation.

DRA promoter

intact cell


Input: Using in vivo genomic footprinting we identified interactions in B-cell lines at the octamer site and the Y, X1, and X2 boxes.

B-cell lines

octamer site


Input: Class II antigen expressing T-cell lines maintained contacts identical to B-cell lines, while class II-negative T-cell lines exhibited no interactions.

Class II antigen expressing T-cell lines

B-cell lines

class II-negative T-cell lines


Input: In lymphoid cell lines, the octamer site is occupied and required for maximal expression.

lymphoid cell lines

octamer site


Input: This is most likely due to the presence of the lymphoid-specific OTF-2 factor.

lymphoid-specific OTF-2 factor


Input: In contrast, the class II-positive nonlymphoid glioblastoma cell line does not exhibit interactions at the octamer site despite the presence of the ubiquitous OTF-1 factor and an open binding site.

class II-positive nonlymphoid glioblastoma cell line

octamer site

open binding site

ubiquitous OTF-1 factor


Input: Thus, the DRA promoter discriminates against OTF-1 activation at the level of DNA binding in the glioblastoma line.

DRA promoter

glioblastoma line


Input: Interferon gamma induces class II expression in this glioblastoma cell line and, in parallel, up-regulates X1 and X2 box protein-DNA interactions, while all other interactions remain unchanged.

Interferon gamma

glioblastoma cell line


Input: These results suggest that interferon gamma functions on a poised promoter by altering weak, nonproductive interactions at the X boxes to strong interactions.

interferon gamma

poised promoter

X boxes


Input: These findings provide direct in vivo evidence to strongly suggest that the modulation of X1 and X2 interactions is an important constituent of the interferon gamma induction pathway.

interferon gamma


Input: Estrogen binding sites in peripheral blood monocytes and effects of danazol on their sites in vitro.

peripheral blood monocytes


Input: This study was designed to investigate the presence of estrogen type I (high affinity, low capacity) and type II (low affinity, high capacity) binding sites in human peripheral blood monocytes and the effects of danazol on these sites.

peripheral blood monocytes


Input: These two types of estrogen binding sites existed in human peripheral blood monocytes.

human peripheral blood monocytes


Input: Danazol bound to these sites in high concentration (10(-6) M, clinical serum concentration during danazol therapy) and decreased the number of both sites.


Input: It is suggested that danazol has an anti-estrogenic action to the monocytes through the competition and suppression of estrogen binding sites as seen in the estrogen target organ.


Input: A microtitre assay system for glucocorticoid receptors: decreased receptor concentration in myocardial infarction.

glucocorticoid receptors


Input: A major difficulty in determination of glucocorticoid receptor sites is the very complicated assay procedure.