| First Author | Meissner F | Year | 2008 |
| Journal | Nat Immunol | Volume | 9 |
| Issue | 8 | Pages | 866-72 |
| PubMed ID | 18604212 | Mgi Jnum | J:137865 |
| Mgi Id | MGI:3803072 | Doi | 10.1038/ni.1633 |
| Citation | Meissner F, et al. (2008) Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat Immunol 9(8):866-72 |
| abstractText | 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. |
