Induction of Fas and Fas-ligand expression in plasmacytoma cells by a cytotoxic factor secreted by murine macrophages.
Induction of tumoricidal activity is one of the major functions of activated macrophages. Our previous study demonstrated that P388D1 murine macrophage-like cells secreted a plasmacytoma cytotoxic factor (PCF) that selectively killed certain tumor cell lines including MOPC-315 plasmacytoma in vitro. Our subsequent studies demonstrated that PCF killed MOPC-315 cells by induction of apoptosis. In this report, the involvement of Fas and Fas ligand (FasL) in PCF-induced apoptosis was investigated. Results suggest that expression of Fas mRNA time-dependently increased in PCF-treated cells and reached an optimal level after 36 h of treatment. The augmented effect of PCF on Fas mRNA expression was significantly reduced by the addition of CB7.C2, an anti-PCF monoclonal antibody. The expression of FasL mRNA was also induced by PCF and reached an optimal level at 24 h, but sharply decreased after 36 h of treatment. Caspase-3 is one of the proteolytic enzymes that can be activated by the Fas-FasL interaction. In our studies, the enzymatic activity of caspase-3 was significantly induced by PCF after 6 h of treatment and reached an optimal level at 12 h. The augmented effect of PCF on caspase activity was significantly reduced by the addition of CB7.C2 and the caspase-3-specific inhibitor, DEVD-fmk. Therefore, PCF-treated plasmacytoma cells might undergo apoptosis via interaction between Fas and FasL.
Chu
C Y
CY
Department of Biology, National Taiwan Normal University, Taipei, Taiwan, ROC.
Tseng
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D003603:Cytotoxins / Q000378:metabolism / Q000494:pharmacology*; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000187:drug effects; D053222:Fas Ligand Protein; D020287:In Situ Nick-End Labeling; D008024:Ligands; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D010954:Plasmacytoma / Q000276:immunology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics
D003603:Cytotoxins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases