Superoxide dismutase 1 regulates caspase-1 and endotoxic shock

被引:252
作者
Meissner, Felix [1 ]
Molawi, Kaaweh [1 ]
Zychlinsky, Arturo [1 ]
机构
[1] Max Planck Inst Infect Biol, Dept Cellular Microbiol, D-10117 Berlin, Germany
关键词
D O I
10.1038/ni.1633
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Caspase-1 serves an essential function in the initiation of inflammation by proteolytically maturing the cytokines interleukin 1 beta and interleukin 18. Several Nod-like receptors activate caspase-1 in response to microbial and 'danger' signals by assembling cytosolic protein complexes called 'inflammasomes'. We show here that superoxide dismutase 1 (SOD1) regulates caspase-1 activation. In SOD1-deficient macrophages, higher superoxide production decreased the cellular redox potential and specifically inhibited caspase-1 by reversible oxidation and glutathionylation of the redox-sensitive cysteine residues Cys397 and Cys362. Conversely, hypoxic conditions abrogated caspase-1 inhibition. In vivo, SOD1-deficient mice produced less caspase-1-dependent cytokines and were less susceptible to lipopolysaccharide-induced septic shock. Our findings identify a physiological post-translational mechanism in the control of caspase-1-mediated inflammatory processes.
引用
收藏
页码:866 / 872
页数:7
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