| Notes
|
A lymphoproliferative disorder could be associated with mutation in this ligand. A lymphoproliferative disorder could be associated with mutation in this ligand. A minimal region of the fasL promoter has been identified containing the transcription start site and a noncanonical c-Myc-binding element, which mediates fasL promoter repression by the activated vitamin D3 receptor in T lymphocytes. A role for the Fas/Fas ligand apoptotic pathway in regulating myeloid progenitor cell kinetics. ATG-induced apoptosis in T cells involves both Fas and TNF pathways and TNF-alpha is produced much earlier than Fas and FasL expression. Abnormal expression and function of Fas ligand of lachrymal glands and peripheral blood was found in Sjogren's syndrome patients with enlarged exocrine glands. An AP-1 site located in the 5' untranslated region of the CD95L gene is required for TCR/CD3-mediated induction of the human CD95L promoter. As brief as a >10-min exposure of human T cells to fibronectin-associated recombinant FasL induces T cell activation and potentiates proinflammatory capacities, e.g., adhesion to extracellular matrix, IFN-gamma secretion, and retention in inflamed areas. Bax, Bcl-2, fas and Fas-L antigen expression in human seminoma: correlation with the apoptotic index. CD95 and/or DR5 can induce apoptosis of CD40-activated chronic lymphocytic leukemia cells. CD95L derived from placenta acts systemically and is primary cause of liver damage in HELLP syndrome. Blocking CD95L can reduce liver cell apoptosis. Strategy may have therapeutic advantages. CD95L, which is found elevated in many human cancer patients, has tumorigenic activities on human cancer cells. CTLA4-FasL fusion protein inhibits the primary mixed leukocyte reaction (MLR), induces specific hyporesponsiveness in the secondary MLR, and may potentially induce hyporesponsiveness by promoting both anergy and apoptosis of alloresponsive clones. Cardiomyocyte necrosis and/or apoptosis via activated tumor necrosis factor (TNF) and the Fas/Fas ligand (FasL) system may be related to the development of ongoing myocardial damage. Cleavage of FasL by MMP-7 occurs at the leucine residues in sequence ""ELAELR"" within the region between the transmembrane and trimerization domains. When this site is unavailable, a ""SL,"" is cleaved. MMP-7 differentially processes murine and human FasL. Cross-talk between glioma cells and neutrophils through the Fas/FasL system stimulated expression of IL-6 and IL-8 in glioma cells, enhanced neutrophil viability, and stimulated cytokine production in neutrophils. Cutaneous T cell lymphoma cells express functional FasL possibly contributing to bystander cytotoxicity within tumor infiltrates. Data report that antagonism of the type 1 insulin-like growth factor receptor in combination with inhibitors of the epidermal growth factor receptor synergistically sensitizes human malignant glioma cells to CD95L-induced apoptosis. Data show that Fas ligand is expressed on cytotoxic effector and memory cells, suggesting that the Fas/FasL system is involved in the inflammatory process observed in silicosis patients. Data strongly indicate that an increment of soluble FAS/soluble FASL ratio after treatment could be an excellent marker of chemosensitivity in colorectal cancer. Data suggest that increased intrathecal release of Fas, but not FasL or caspase 3, in the cerebrospinal fluid of infants with hydrocephalus may serve as an indicator of brain injury from progressive ventricular dilatation. Differential expressions of Fas and Fas ligand in human placenta. Differential secretion of Fas ligand microvesicles during activation-induced death of T cells. Effect of hibuscus polyphenol extracs in human gastric carcinoma cells is mediated via p53 signaling and p38 MAPK/FasL cascade pathway. Ets-1 and Sp1 have a role in regulating FasL expression in human vascular smooth muscle cells. Expression of Fas and Fas ligand in esophageal tissue mucosa and carcinomas. Expression of FasL gene in T cells of renal allograft recipients. FASL secretion was analyzed in melanoma cells in culture. The secretion was associated with secretory vesicles upon melanoma activation with phytohemagglutonins or alpha-MSH. Fas and Fas ligand expression in leukocytes during systemic inflammation. Fas and FasL have roles in progression of breast cancer. Fas and TRAIL play an important role in the H. pylori-mediated apoptosis of gastric epithelial cells. Fas engagement with Fas ligand induced activation of Akt and upregulation of endothelial nitric oxide synthase expression without induction of apoptosis. Fas ligand increases Kv1.3 channel activity through the same canonical apoptotic signaling cascade that is required for potassium efflux, cell shrinkage, and apoptosis. Fas ligand is an apoptotic pathway of hepatocellular carcinoma cells. Fas ligand is not constitutively expressed in normal peripheral blood or neoplastic B lymphocytes. Fas system as an inducer of apoptosis in cutaneous leishmaniasis. Fas-FasL interactions may contribute to mechanisms of neuronal loss and neuritic degeneration in Alzheimer disease. Fas-L expression may be associated with the escape from of immunal surveillance. Fas/Fas-L and Bcl-2 expression participate in regulation of apoptosis in extravillous trophoblast(EVT) along invasion to decidua. Increased apoptosis in invasive phenotype of EVT may be attributable to increased Fas and Fas-L and decreased Bcl-2. Fas/FasL pathway can be employed by monocytes/macrophages to induce VSMC apoptosis in the atherosclerotic lesions. FasL blocks expression of CD28 at the transcriptional level. FasL induces NF-kappaB activation and IL-8 production by a novel mechanism, distinct from that of TNF-alpha. FasL is implicated in differentiation, growth, invasion and metastasis of gastric cancer by inducing apoptosis of infiltrating lymphocytes. FasL is produced by and stored in the first trimester human syncytiotrophoblasts only and they lack surface membranal FasL. FasL protein is an important mediator of apoptosis. FasL protein levels show that C57BL/10 cortical cultures are more resistant to death receptor-mediated apoptotic cell death as compared to C57BL/6 strain mice. FasL-mediated cytotoxicity is regulated by the FasL cytoplasmic tail. Genetic polymorphisms of FasL (CD178) in human longevity. HIV Tat binds Egr proteins and enhances Egr-dependent transactivation of the Fas ligand promoter. Heart graft biopsies haveelevated FasL mRNA expression levels compared to the expression levels before and after acute rejection. High levels of Max and stress-induced NFkappaB activation may result in elevated expression of Fas ligand in human lung cancer cells and possibly contribute to Fas ligand-associated immune escape mechanisms. In transgenic mice, the human FASL promoter induces reporter expression in intestinal epithelial cells. Non-lymphoid FasL is expressed in response to peripheral T cell activation & regulates T cells that infiltrate peripheral tissues. Induction of FasL expression by adhesion of endometrial stromal cells to the extracellular matrix may take part in the development of immunotolerance by inducing apoptosis of cytotoxic T lymphocytes. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. JNK/p38 > c-Jun > Fas ligand > Fas pathway plays an important role in mediating cisplatin-induced apoptosis in ovarian cancer cells. Lethal cytokines, such as FasL, may contribute to peritoneal cell turnover and the loss of mesothelium in peritoneal dialysis. Levels in CSF are elevated in in neuro-Behcet's disease. Longitudinal data indicate that FasL mRNA increases in peripheral blood mononuclear cells of multiple sclerosis (MS) patients, especially during the secondary progressive course, and is downregulated during clinical activity in relapsing remitting MS. Modulation of FasL by placental as well as maternal hormonal milieu induces apoptosis in decidual cells, glandular cells, and immune cells, facilitating trophoblast invasion and peritrophoblastic immunotolerance. Mouse cells expressing human membrane-bound, but not soluble, Fas ligand induce inflammation in vivo. NF-kappaB activation and FasL overexpression occur in PBMCs and atherosclerotic lesions of patients with carotid stenosis. The NF-kappaB-FasL pathway could be involved in the mechanisms underlying plaque instability in humans. Our data indicate an associaton between premature rupture of membranes and increased prevalence of neonatal AG genotype at -670 Fas promoter gene. Plasma levels may be a marker for chronic hepatitis C infections. Progesterone-induced apoptosis in immortalized normal and malignant HOSE cells involves enhanced expression of FASL. Regulation of fas ligand expression by IL-8 in human endometrium. Results show that FasL in endometrial stromal cells in culture has a cyclic expression model, suggesting that there may be a regulation at the translation level. Serum levels may be affected by insulin resistance, but is not an effective markers of silent myocardial ischemia in type 2 diabetes. Significantly lower soluble form of fas is associated with bile duct carcinoma. Somatostatin receptor subtype 2 sensitizes human pancreatic cancer cells to ligand-induced apoptosis. Supernatants from T cell blasts, pulse-stimulated with phytohemagglutinin contained FasL expressed on microvesicles. T cells from systemic lupus erythematosus patients kill autologous monocytes through apoptotic pathways involving the ligand FasL. The Fas ligand may be involved in the apoptosis of astrocytic tumors, and the apoptotic index can be a useful parameter for assessing prognosis of astrocytic tumors. The FasL expressed in human colon cancer cells may be regulated by endogenous factors in the microenvironment of the host and facilitate the escape of tumor cells from the host immune system. The combination of some polymorphisms of Fas or FasL significantly influenced CD4+ T cell production and viral load decrease, showing that these genes can play a role in the immunoreconstitution triggered by antiretroviral therapy. The endometrial cells expressed Fas and low levels of FasL. The expression of FasL is upregulated in colon cancer and the functionally expressed FasL can induce apoptosis of Fas-expressing T lymphocytes. The extracellular domains of FasL are sufficient to drive membrane FasL-induced formation of supramolecular Fas-FasL complexes, whereas soluble FasL-induced Fas aggregation is dependent on lipid rafts and the intracellular domain of Fas. The frequent expression and coexpression of Fas, FasL, and c-FLIP in urothelial carcinomas implicates c-FLIP as an inhibitor of the Fas-FasL-induced death pathway in these tumors. The function of endothelial FasL during atherosclerosis was studied in APOE(-) mice transgenic for human FasL. Overexpression of endothelial FasL is antiinflammatory and inhibits atherosclerosis under hypercholesterolemic conditions. The human papillomavirus type 16 E5 protein impairs TRAIL- and FasL-mediated apoptosis in HaCaT cells by different mechanisms. The observed impact of FasL on adhesion and transendothelial migration provides evidence for novel biological functions of FasL. The protein encoded by this gene is the ligand for FAS. Both are transmembrane proteins. Interaction of FAS with this ligand is critical in triggering apoptosis of some types of cells such as lymphocytes. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). The results indicate that FasL inhibition by all-trans-RA involves a novel mechanism whereby the transcriptional function of NFAT is blocked. The sensitivity of FasL expressing tumor cells to lysis by cytotoxic T-cells was similar to that of FasL non-expressors. These results support a role for Egr-1, -2, and -3 in nonlymphoid expression of Fas ligand, TRAIL, and tumor necrosis factor. This review considers the role of the FasL-Fas system as a double-edged sword in the central nervous system: maintaining the immune suppressed status in normal brain and inducing neuronal cell death and inflammation in a variety of neurologic disorders. Through the high and sustained expression of FasL that is transcriptionally regulated, synovial gamma delta T cells of the V delta 1 subtype may efficiently lyse a wide variety of cell types at sites of inflammation. To evaluate the impact of genetic variations to apoptosis during progression of acquired immunodeficiency syndrome (AIDS), we have performed an extensive genetic analysis of Fas and Fas ligand ( FasL) genes. To see if variants of the FasL gene played a role in Hashimoto's thyroiditis and Graves' disease, 2 FasL polymorphisms (C -843 T in the promoter, A IVS2nt-124 G in intron 2)were studied. No association was found. Toxic epidermal necrolysis and Stevens-Johnson syndrome are induced by this protein. Up-regulation in highly malignant multiple myeloma plasma cells negatively regulates erythroblast maturation; a major pathogenetic mechanism of anemia in multiple myeloma. Up-regulation of FasL expression plays an important role in invasive depth, histological classification and metastasis of gallbladder carcinoma. We evaluate a family with 4 of its 5 members harboring a mutation causing skipping of exon-6; ALPS in one male patient was caused by haploinsufficiency of membrane CD95 expression. Our data challenge the hypothesis that sCD95 causes autoimmunity. Western blot analysis showed that butyrate increased Fas and Fas ligand levels in butyrate-induced apoptosis. A linear pathway for Nef-induced FasL expression that encompasses p38 and AP-1 has been elucidated. Furthermore, chemical inhibition of the p38 pathway attenuates HIV-1-mediated bystander killing of CD8 cells in vitro. Activated langerhan's cells are capable of expressing CD95-L in a functional location, thus bearing the potential to exert tolerogenic capabilities against CD95-expressing T cells. Activation of p38 MAPK and c-Jun N-terminal kinase pathways by hepatitis B virus X protein mediates apoptosis via induction of Fas/FasL and TNFR1/TNFa expression. Addition of IL-12 might increase the efficacy of IL-2 immunotherapy by inhibition of the IL-10-mediated negative feed-back loop on IL-2-mediated sFasL release. Apoptosis by FasL-dependent ligation is not modulated by Bcl-2 in vivo. Apoptosis mediated by Fas-FasL and engagement of CTLA-4 are involved in modulation of the immune response in patients infected with Paracoccidioides brasiliensis. Cytokine-induced trophoblast apoptosis is mediated in part by the FasL/Fas pathway, suggesting that cytokines promote sensitivity to Fas-mediated apoptosis. Evaluation of the FasL gene FASL on chromosome 1q23 as a candidate susceptibility gene for Type I diabetes. Examined the correlation between injury of the hepatocytes and mRNA expression of FasL and perforin/granzyme B in liver tissue to investigate the roles of both the FasL and the perforin/granzyme B pathways in chronic hepatitis B. Expressed during acute cellular rejection episodes after kidney transplantation. Expression and function in human urinary bladder transitional cell carcinomas; correlates with tumor progression. Expression and function of fas ligand in human myeloid leukemia cells. Expression levels in hepatocellular carcinoma, compard with HBxAg levels. Expression of CD95 in 15/17 human melanoma cell lines analysed, but complete lack of CD95 ligand (CD95L). Expression was found mainly on astrocytes and microglial cells; no significant difference between cases with and without pontosubicular neuron necrosis. Fas ligand is up-regulated in acute lung injury and the acute respiratory distress syndrome. FasL gene expression is induced by Hepatitis B virus X protein through enhancing transcriptional activity of Egr-2 and Egr-3. Findings support the hypothesis that the expression of FasL in normal ovary is hormonally sensitive. Hepatitis C virus core protein plays a role in the induction of functional FasL in a hepatoblastoma cell line. Homeostatic regulation of myelopoiesis in bone marrow is mediated via an autoregulatory feedback loop via the Fas-FasL pathway. Induction of CD95/CD95L expression does not have a role in p53-induced apoptosis. Inhibiton of CD95L expression by vitamin E. Membrane-associated FasL is pro-apoptotic, whereas mFasL can be released from T lymphocytes. Physiological function of human sFasL is to delete the potentially auto-reactive ""memory"" lymphocytes. Results showed that Fas and/or Fas-Ligand, Bcl-2, and tissue transglutaminase may be involved in apoptotic pathways leading to mucosal atrophy in children with coeliac disease. Results suggest that p21 and FasL gene activation is required for myeloid leukemia cell survival or maturation but not for cell death via Sp1 and NFkappaB as regulators of these genes. SFasL and matrilysin are expressed in seminal plasma and have a role in regulation of the function of the Fas system. SFasL may be involved in either induction of apoptosis or autoimmune diseases. Serum and peritoneal fluid of women with moderate to severe endometriosis contain elevated concentrations of soluble Fas ligand compared to women with minimal or mild endometriosis and women without endometriosis. Serum sFasL in biliary disease may be derived predominantly from activated immune cells and not from cancer cells. The role of Fas/Fas ligand (FasL) in tum orgenesis, immune escape, counterattack in colonic cancer. The trans-activation ability of Tat at the long terminal repeat does not correlate with T cell apoptosis but that the ability of Tat to up-regulate CD178 mRNA expression and induce apoptosis in T cells is critically dependent on the C terminus of Tat. Tranduces, in synergy with non-cytotoxic anti-Fas monoclonal antibody (mAb), signals for apoptosis and nuclear translocation of the NF-kappaB (p65/p50) heterodimer. Trophoblast-cytokine-Fas/FasL triad"" determines the ability of the Fas/FasL system to regulate trophoblast viability. Upregulation of Fas by IFN-gamma in SNU-638 may accelerate the apoptosis pathway through the Fas and FasL interaction between gastric cancer cells and immune cells. Upregulation of mesangial FasL may contribute to the glomerular inflammation in proliferative lupus nephritis.
|