*  ERK mediated upregulation of death receptor 5 overcomes the lack of p53 functionality in the diaminothiazole DAT1 induced...

Oncogenic Ras sensitizes normal human cells to tumour necrosis factor-alpha-related apoptosis-inducing ligand-induced apoptosis ... Furthermore, DAT1 was found to be more active in inducing apoptosis in colon cancer cell lines where the small GTPase protein ... Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L. Death receptor 5, a new member of the TNFR family, and DR4 ... p53-independent upregulation of KILLER/DR5 TRAIL receptor expression by glucocorticoids and interferon-gamma. Exp Cell Res. ...

*  TNFRSF1B Gene - GeneCards | TNR1B Protein | TNR1B Antibody

Protein Coding), TNF Receptor Superfamily Member 1B, including: function, proteins, disorders, pathways, orthologs, and ... Among its related pathways are TRAF Pathway and PEDF Induced Signaling. GO annotations related to this gene include ubiquitin ... Protein Domains for TNFRSF1B Gene. Blocks:. * TNFR/CD27/30/40/95 cysteine-rich region ... Protein details for TNFRSF1B Gene (UniProtKB/Swiss-Prot). Protein Symbol:. P20333-TNR1B_HUMAN. Recommended name:. Tumor ...

*  Establishment and characterization of a sustained delayed-type hypersensitivity model with arthritic manifestations in C57BL/6J...

In the murine collagen-induced arthritis (CIA) model, disease is induced by immunization with type II collagen (CII) in an ... Mean ± SEM is shown (n = 5 per time point). (g) Serum levels of acute-phase protein serum amyloid P component (SAP) on selected ... Bevaart L, Vervoordeldonk MJ, Tak PP: Evaluation of therapeutic targets in animal models of arthritis: how does it relate to ... The glucocorticoid dexamethasone was administered in doses of 1 mg/kg from the time of disease onset and was able to ...

(1/166) Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR.

The tumor necrosis factor (TNF) and TNF receptor (TNFR) gene superfamilies regulate diverse biological functions, including cell proliferation, differentiation, and survival [1] [2] [3]. We have identified a new TNF-related ligand, designated human GITR ligand (hGITRL), and its human receptor (hGITR), an ortholog of the recently discovered murine glucocorticoid-induced TNFR-related (mGITR) protein [4]. The hGITRL gene mapped to chromosome 1q23, near the gene for the TNF homolog Fas/CD95 ligand [5]. The hGITR gene mapped to chromosome 1p36, near a cluster of five genes encoding TNFR homologs [1] [6]. We found hGITRL mRNA in several peripheral tissues, and detected hGITRL protein on cultured vascular endothelial cells. The levels of hGITR mRNA in tissues were generally low; in peripheral blood T cells, however, antigen-receptor stimulation led to a substantial induction of hGITR transcripts. Cotransfection of hGITRL and hGITR in embryonic kidney 293 cells activated the anti-apoptotic transcription factor NF-kappaB, via a pathway that appeared to involve TNFR-associated factor 2 (TRAF2) [7] and NF-kappaB-inducing kinase (NIK) [8]. Cotransfection of hGITRL and hGITR in Jurkat T leukemia cells inhibited antigen-receptor-induced cell death. Thus, hGITRL and hGITR may modulate T lymphocyte survival in peripheral tissues.  (+info)

(2/166) CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor.

CD4(+)CD25(+) immunoregulatory T cells represent a unique lineage of thymic-derived cells that potently suppress both in vitro and in vivo effector T cell function. We analyzed CD4(+)CD25(+) and CD4(+)CD25(-) T cells by DNA microarray, identifying 29 genes differentially expressed in the resting subpopulations, and 77 that were differentially expressed following activation. Most of these genes were elevated in the CD4(+)CD25(+) population, suggesting a previously activated phenotype. Among these were a number of genes that antagonize signaling, including members of the SOCS family, which may contribute to their anergic phenotype. Multiple cell surface receptors also had increased expression in CD4(+)CD25(+) cells, including GITR, a member of the TNF receptor superfamily. Importantly, antibodies to GITR abrogated suppression, demonstrating a functional role for this receptor in regulating the CD4(+)CD25(+) T cell subset.  (+info)

(3/166) Recombinant glucocorticoid induced tumor necrosis factor receptor (rGITR) induces NOS in murine macrophage.

Glucocorticoid induced tumor necrosis factor receptor (GITR) is a new member of the tumor necrosis factor-nerve growth factor receptor superfamily of which the function has not been well studied. The extracellular domain of GITR was produced in Escherichia coli and purified as a single band of predicted M(r) of 18.0 kDa. GITR and GITR ligand were expressed constitutively on the surface of Raw 264.7 macrophage cell line and murine peritoneal macrophages. An extracellular domain of GITR can activate murine macrophages to express inducible nitric oxide synthase and to generate nitric oxide in a dose- and time-dependent manner.  (+info)

(4/166) Role of GITR in activation response of T lymphocytes.

In this study, we describe the generation and characterization of mice in which GITR gene (TNFRSF18 [tumor necrosis factor receptor superfamily 18]), a member of the TNFRSF expressed mainly on T lymphocytes, has been ablated (GITR(-/-) mice). Results indicate that GITR inactivation does not impair the normal development of the lymphoid organs but modulates T-cell activation. In fact, when GITR(-/-) T lymphocytes are activated by treatment with an anti-CD3 monoclonal antibody they proliferate more than wild-type cells. Moreover, activated GITR(-/-) T lymphocytes express higher levels of interleukin-2 receptor, produce larger amounts of interleukin-2, and are more sensitive to activation-induced cell death than controls. These results suggest that GITR is involved in the regulation of T-cell receptor/CD3-driven T-cell activation and programmed cell death.  (+info)

(5/166) Inhibition of human CD4(+)CD25(+high) regulatory T cell function.

CD4(+)CD25(+high) T cells are potent regulators of autoreactive T cells. However, it is unclear how regulatory CD4(+)CD25(+high) cells discriminate between desirable inflammatory immune responses to microbial Ags and potentially pathologic responses by autoreactive T cells. In this study, an in vitro model was created that allowed differential activation of regulatory CD4(+)CD25(+high) and responder CD4(+) T cells. If CD4(+)CD25(+high) regulatory cells were strongly activated, they maintained suppressive effector function for only 15 h, while stimulation with weaker TCR stimuli produced regulatory cells that were suppressive until 60 h after activation. In contrast, strongly activated CD4(+) responder T cells were resistant to regulation at all time points, while weakly stimulated CD4(+) cells were sensitive to suppression until 38 or 60 h after activation depending upon the strength of the stimulus. The extent of suppression mediated by CD4(+)CD25(+high) cells also depended on the strength of stimulation in an Ag-specific system. Thus, the stronger the TCR signal, the more rapidly and more completely the responder cells become refractory to suppression.  (+info)

(6/166) Regulation of murine inflammatory bowel disease by CD25+ and CD25- CD4+ glucocorticoid-induced TNF receptor family-related gene+ regulatory T cells.

CD4(+)CD25(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance and prevention of autoimmune disease. However, accumulating evidence suggests that a fraction of the peripheral CD4(+)CD25(-) T cell population also possesses regulatory activity in vivo. Recently, it has been shown glucocorticoid-induced TNFR family-related gene (GITR) is predominantly expressed on CD4(+)CD25(+) regulatory T cells. In this study, we show evidence that CD4(+)GITR(+) T cells, regardless of the CD25 expression, regulate the mucosal immune responses and intestinal inflammation. SCID mice restored with the CD4(+)GITR(-) T cell population developed wasting disease and severe chronic colitis. Cotransfer of CD4(+)GITR(+) population prevented the development of CD4(+)CD45RB(high) T cell-transferred colitis. Administration of anti-GITR mAb-induced chronic colitis in mice restored both CD45RB(high) and CD45RB(low) CD4(+) T cells. Interestingly, both CD4(+)CD25(+) and CD4(+)CD25(-) GITR(+) T cells prevented wasting disease and colitis. Furthermore, in vitro studies revealed that CD4(+)CD25(-)GITR(+) T cells as well as CD4(+)CD25(+)GITR(+) T cells expressed CTLA-4 intracellularly, showed anergic, suppressed T cell proliferation, and produced IL-10 and TGF-beta. These data suggest that GITR can be used as a specific marker for regulatory T cells controlling mucosal inflammation and also as a target for treatment of inflammatory bowel disease.  (+info)

(7/166) Induction of nitric oxide synthase (NOS) by soluble glucocorticoid induced tumor necrosis factor receptor (sGITR) is modulated by IFN-gamma in murine macrophage.

Earlier study showed that glucocorticoid induced tumor necrosis factor receptor (GITR), a new TNFR family, activated murine macrophages to express inducible nitric oxide synthase (iNOS) and to generate nitric oxide (NO). A possible involvement of pro-inflammatory cytokines on NO production by GITR was investigated in vitro systems and signaling molecules contributing to sGITR-induced iNOS production are determined in Raw 264.7 cells, a murine macrophage cell line. The result showed that the synergy was afforded by the combination of GITR with IFN-g in a dose-dependent manner but IFN-gamma alone was not able to induce NOS. No effects were observed with TNF-alpha, IL-1beta, or IL-6 co-treated with GITR. To determine signaling molecules contributing to sGITR-induced iNOS production, a specific inhibitor for signal pathway proteins tested showed that PDTC (NF-kappaB) and genistein (tyrosine kinase) inhibited NOS induction significantly, while sodium orthovanadate (tyrosine phosphatase) potentiated NOS expression. These results suggest that activations of NF-kappaB were involved in induction of iNOS by GITR and IFN-gamma priming caused earlier and stronger NF-kappaB activation.  (+info)

(8/166) Soluble glucocorticoid-induced TNF receptor (sGITR) induces inflammation in mice.

Glucocorticoid-induced TNF receptor (GITR) was a new member of the TNF/nerve growth factor receptor (TNFR/ NGFR) family and induced in murine T cells by dexamathasone. Recombinant soluble GITR (sGITR) induced an inflammation in peritoneal membrane and changes in spleen after i.p. injection of 3 mg/kg in C57BL/6 mice. Spleen was enlarged and percentage of neutrophils and monocytes were increased. The area of red pulp in spleen was increased, while that of white pulp was decreased after GITR injection. The thickening of membrane and neutrophil infiltration was observed in peritoneal membrane with increased myeloperoxidase activity. At later time, neutrophil infiltration moved to inside the tissue with tissue damage. GITR ligand and GITR were expressed constitutively on the surface of spleen cells and cells from peritoneal fluid. In contrast, no significant change in the spleen and in peritoneal membrane was observed in mice treated with LPS. GITR may play a role in body's inflammatory processes.  (+info)


  • p53 is a tumour suppressor protein that plays a key role in many steps of apoptosis, and malfunctioning of this transcription factor leads to tumorigenesis. (biomedcentral.com)
  • Further, DAT1 is more efficient to induce apoptosis in colon cancer cells with mutated Ras or Raf. (biomedcentral.com)
  • The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. (genecards.org)
  • Knockout studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways. (genecards.org)
  • Isoform 2 blocks TNF-alpha-induced apoptosis, which suggests that it regulates TNF-alpha function by antagonizing its biological activity. (genecards.org)


  • Among its related pathways are TRAF Pathway and PEDF Induced Signaling . (genecards.org)


  • We demonstrate that DTH-arthritis could be induced in C57BL/6 mice with paw swelling lasting for at least 28 days and that disease induction was dependent on CD4 + cells. (biomedcentral.com)


  • p53 is a tumour suppressor protein that plays a key role in the cellular response to stress and hence acts as a major obstructer of tumorigenesis. (biomedcentral.com)