Disease relevance of Faslg

• CD95 plays a physiological role in the regulation of the immune response; furthermore, alterations in CD95/CD95L function may contribute to the pathogenesis of a number of human diseases, including cancer, autoimmune diseases and viral infections [1].
• Modulation of experimental allergic encephalomyelitis in Lewis rats by administration of a peptide of Fas ligand [2].
• Moreover, STAT-1 is critical for the induction of Fas receptor and Fas ligand expression by ischemia/reperfusion (I/R) [3].
• The Fas/Fas ligand system is involved in the pathogenesis of autoimmune myocarditis in rats [4].
• Expression of Fas and Fas ligand after experimental traumatic brain injury in the rat [5].

Psychiatry related information on Faslg

• Fas and Fas ligand expression in Alzheimer's disease [6].

High impact information on Faslg

• Spleen, but not thymus DC, were able to kill the NK-sensitive YAC-1 cell line in vitro, and since this killing was Ca2+ dependent, a Fas ligand-Fas interaction was probably not involved [7].
• Upon CdCl(2)-treatment, both Sertoli cells and the germ cells upregulated Fas ligand; this event was also suppressed by zinc protoporphyrin-IX and restored by dichloromethane [8].
• A targeted DNA vaccine encoding fas ligand defines its dual role in the regulation of experimental autoimmune encephalomyelitis [9].
• This study used naked DNA vaccination to induce breakdown of tolerance to self and thus elicit immunological memory to native, membrane-bound Fas ligand (FasL) [9].
• This study was undertaken to (a) determine if UDCA inhibits apoptosis from deoxycholic acid (DCA), as well as from ethanol, TGF-beta1, Fas ligand, and okadaic acid; and to (b) determine whether mitochondrial membrane perturbation is modulated by UDCA [10].

Chemical compound and disease context of Faslg

• Induction of apoptosis and Fas receptor/Fas ligand expression by ischemia/reperfusion in cardiac myocytes requires serine 727 of the STAT-1 transcription factor but not tyrosine 701 [3].
• Apoptosis induced by penta-acetyl geniposide in C6 glioma cells is associated with JNK activation and Fas ligand induction [11].
• Both Kupffer cells and LPS/Kupffer cell-conditioned supernatants induced expression of Fas and Fas ligand on malignant glioma cells [12].
• Nitric oxide mediates apoptosis through formation of peroxynitrite and Fas/Fas-ligand interactions in experimental autoimmune uveitis [13].

Biological context of Faslg

• Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis [14].
• When ONOO(-) was added after induction of CD95-tyrosine phosphorylation by CD95L or hyperosmolarity, tyrosine nitration of CD95 was largely prevented and death-inducing signaling complex formation occurred [15].
• CONCLUSION: This down-regulation of CD95L and TNF-alpha in allografts rendered tolerant by donor-specific transfusion suggests a role for apoptosis-inducing pathways in acute allograft rejection [16].
• H(2)O(2) induces upregulation of Fas and Fas ligand expression in NGF-differentiated PC12 cells: modulation by cAMP [17].
• Fas-ligand (FasL) plays a critical role in activation-induced cell death of activated cytotoxic lymphocytes [18].

Anatomical context of Faslg

• Hyperosmolarity triggers CD95 membrane trafficking and sensitizes rat hepatocytes toward CD95L-induced apoptosis [19].
• Corticotropin-releasing hormone induces Fas ligand production and apoptosis in PC12 cells via activation of p38 mitogen-activated protein kinase [20].
• Here we asked whether Fas/Fas ligand system interacts with NO using rat granulosa cell culture [21].
• First we tested the effect of two pharmacological PI 3-kinase inhibitors, wortmannin and LY294002, on CD95 agonistic antibody-induced apoptosis in three different cell lines [1].
• Cross-Talk between Fas/Fas ligand system and nitric oxide in the pathway subserving granulosa cell apoptosis: a possible regulatory mechanism for ovarian follicle atresia [21].

Associations of Faslg with chemical compounds

• CD95L addition under normoosmotic conditions caused CD95 membrane trafficking, which was sensitive to JNK inhibition, but not to cyclic adenosine monophosphate or inhibition of PKC, Erks, and p38(MAPK) [19].
• These effects were mediated by the CRH type 1 receptor because its antagonist antalarmin blocked CRH-induced apoptosis and Fas ligand expression [20].
• Doxorubicin activates nuclear factor of activated T-lymphocytes and Fas ligand transcription: role of mitochondrial reactive oxygen species and calcium [22].
• The role of the Fas/Fas ligand system in estrogen-induced thymic alteration [23].
• The effect of lipopolysaccharide (LPS) on the expression of CD95 (APO-1/Fas) receptor and ligand (CD95L) was studied in primary cultures of rat liver Kupffer cells (KCs), sinusoidal endothelial cells (SECs), and parenchymal cells (PCs) at the messenger RNA (mRNA) level and by means of immunocytochemistry [24].

Physical interactions of Faslg

• Fas ligand (FasL) induces apoptotic cell death when bound to Fas antigen [25].
• RESULTS: Retinal detachment resulted in the time-dependent formation of the FAS-receptor/FAS-ligand complex that preceded the peak of caspase-9 activity and caspase-9/cytochrome c complex formation [26].

Regulatory relationships of Faslg

• CRH induced Fas ligand production and apoptosis [20].
• We initially established that both transient and constitutive Notch3 signaling promoted VSMC survival in response to the proapoptotic Fas ligand (FasL) [27].
• Over the past few years, a number of experimental evidences suggested the involvement of Fas Ligand (FasL) expressing Sertoli cells to induce apoptosis of Fas bearing germ cells [28].
• These findings indicate that apoptosis of skeletal muscle in TA-induced myopathy may be triggered by Fas-Fas ligand signals and promoted mainly by overexpression of the pro-apoptotic molecules of FADD and caspase 8 involving the extrinsic pathway [29].
• BACKGROUND: The aim of this study was to evaluate the role of the pro-apoptotic molecule Fas Ligand (FasL) in 120 min normothermic ischemia-reperfusion (I-R) induced apoptosis in rat liver treated or not with Z-Asp-cmk caspase inhibitor [30].

Other interactions of Faslg

• In the tolerated allografts, however, levels of graft-infiltrating cell apoptosis and CD95L and TNF-alpha expression during the same period of time were dramatically lower [16].
• Hyperosmolarity, however, sensitized hepatocytes toward CD95L-induced apoptosis, as assessed by annexin V staining and terminal deoxynucleotidyl transferase-mediated X-dUTP nick-end labeling (TUNEL) assay [19].
• Pretreatment of hepatocytes with ONOO(-) inhibited CD95L- and hyperosmolarity-induced CD95 membrane trafficking and formation of the death-inducing signaling complex, but not epidermal growth factor receptor activation and its association with CD95 [15].
• We have previously demonstrated by FACS analysis and histochemistry that Fas ligand (FasL) increases on cochlear cell surfaces after immune response or stimulation with gamma-interferon (IFN-gamma) [31].
• Expression of Fas ligand (FasL), an AP-1 transcriptional target, increased during accelerated cell death [32].

Analytical, diagnostic and therapeutic context of Faslg

• Recently, conflicting studies have been published concerning the expression and the role of CD95L in allograft rejection and tolerance [16].
• RESULTS: In the acutely rejected allografts, a peak in the expression of CD95L and TNF-alpha and in the number of apoptotic cells was observed during the first week after transplantation; apoptotic cells were confined to graft-infiltrating cells [16].
• Real-time RT-PCR revealed an increase in mRNA levels of Fas ligand (Fas-L), a membrane protein related to the TNF family, in cultured microglia following OGD exposure [33].
• Exogenous Expression of Fas-Ligand or CrmA Prolongs the Survival in Rat Liver Transplantation [18].
• By Western blot it was determined that the levels of Fas ligand protein were increased in the CD8-depleted group compared with those in control and FK506-treated allograft recipients [34].

References