Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand.
Fas ligand is a well-characterized apoptosis inducer. Here we demonstrate that Fas ligand induces the processing and secretion of interleukin-1beta (IL-1beta) in peritoneal exudate cells. This IL-1beta secretion is independent of IL-1beta converting enzyme (caspase 1), yet it is inhibited by caspase inhibitors, indicating that a caspase(s) in addition to IL-1beta converting enzyme can process IL-1beta. Inoculation of tumor cells expressing Fas ligand into wild-type mice induces a massive neutrophil infiltration that is, in contrast, suppressed in IL-1alpha/beta knockout mice. These results demonstrate a newly discovered role for Fas ligand in inflammation, and challenge the dogma that apoptosis does not induce inflammation.
Miwa
K
K
Osaka Bioscience Institute, Department of Molecular Biology, Suita, Japan.
Asano
M
M
Horai
R
R
Iwakura
Y
Y
Nagata
S
S
Suda
T
T
D000818:Animals; D017209:Apoptosis; D020170:Caspase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003433:Crosses, Genetic; D053222:Fas Ligand Protein; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology; D006720:Homozygote; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D019014:fas Receptor; D020170:Caspase 1