Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand.

Miwa, K; Asano, M; Horai, R; Iwakura, Y; Nagata, S; Suda, T · Nat Med · 1998

basic_science · Level V

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Abstract

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.

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