Nature Medicine
4, 1287 - 1292 (1998)
doi:10.1038/3276
Caspase 1-independent IL-1 release and inflammation induced by
the apoptosis inducer Fas ligandKeiko Miwa1, Masahide Asano2, Reiko Horai2, Yoichiro Iwakura2, Shigekazu Nagata1, 3
& Takashi Suda1, 41
Osaka Bioscience Institute, Department of Molecular
Biology, Suita, Osaka 565-0874,
Japan
2
The University of Tokyo, The Institute of Medical Science,
Laboratory Animal Research Center, Minato-ku, Tokyo
108-8639, Japan
3
Osaka University Medical School, Department of Genetics
, Suita, Osaka 565-0871, Japan
4
Kanazawa University, Cancer Research Institute, Center
for the Development of Molecular Target Drugs, Kanazawa,
Ishikawa 920-0934, Japan
Correspondence should be addressed to Takashi Suda sudat@kenroku.kanazawa-u.ac.jp
Fas ligand is a well-characterized apoptosis inducer. Here we demonstrate
that Fas ligand induces the processing and secretion of interleukin-1
(IL-1) in peritoneal exudate cells. This IL-1 secretion is independent
of IL-1 converting enzyme (caspase 1), yet it is inhibited by caspase
inhibitors, indicating that a caspase(s) in addition to IL-1 converting
enzyme can process IL-1. Inoculation of tumor cells expressing Fas ligand
into wild-type mice induces a massive neutrophil infiltration that is, in
contrast, suppressed in IL-1 / 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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