Fas/Fas ligand interactions are involved in ultraviolet-B-induced human lymphocyte apoptosis.
We wondered whether the apoptosis known to occur after UV-B irradiation might involve the Fas/Fas ligand (FasL) signaling pathway. We exposed PBLs from normal individuals, and also the Jurkat (E6-1) and U937 cell lines, to graded doses of UV-B irradiation and observed a prompt and marked increase in Fas expression at doses as low as 0.5 mJ/cm2. Increased Fas expression did not require new protein synthesis, since cycloheximide-treated cells also showed an increase in Fas after UV-B. UV-B-irradiated cells cultured in the presence of zinc showed inhibition of apoptosis coincident with a marked increase in Fas+ cells, apparently indicating the accumulation of Fas-bearing cells unable to undergo apoptosis. After UV-B irradiation, PBLs showed increased expression of Fas ligand; the E6-1 lymphocytic cell line also released soluble FasL. UV-B induced apoptosis could be partially blocked by neutralizing FasL Abs, and a FasL-resistant variant of E6-1 cell line showed reduced apoptosis after UV-B irradiation, implying that the increase in Fas expression signified a role for Fas in UV-induced apoptosis. UV-induced Fas expression may serve to target stress-injured cells for removal by FasL-bearing cells or by FasL produced by the cells themselves in response to the stimuli, and may represent a general function of the Fas/FasL pathway in facilitating the apoptosis and elimination of undesirable or harmful cells.
Caricchio
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Department of Medicine, University of North Carolina at Chapel Hill 27599, USA.
Reap
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Cohen
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D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology* / Q000528:radiation effects*; D002470:Cell Survival / Q000276:immunology / Q000528:radiation effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D053222:Fas Ligand Protein; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007113:Immunity, Innate; D019169:Jurkat Cells; D008024:Ligands; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D016403:Lymphoma, Large B-Cell, Diffuse; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects; D012995:Solubility; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D015032:Zinc / Q000494:pharmacology; D019014:fas Receptor / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects
D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007106:Immune Sera; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D003513:Cycloheximide; D015032:Zinc