| First Author | Kono H | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 7 | Pages | 3734-40 |
| PubMed ID | 22914048 | Mgi Jnum | J:190231 |
| Mgi Id | MGI:5448472 | Doi | 10.4049/jimmunol.1200136 |
| Citation | Kono H, et al. (2012) The IL-1-dependent sterile inflammatory response has a substantial caspase-1-independent component that requires cathepsin C. J Immunol 189(7):3734-40 |
| abstractText | The sterile inflammatory response to cell death and irritant crystals is medically important because it causes disease. Although these stimuli are structurally distinct, they cause inflammation through a common pathway that requires the cytokine IL-1. In vitro, the inflammasome, and in particular its generation of active caspase-1, is absolutely required to produce bioactive IL-1beta. However, in this study, we report that caspase-1 is not required in vivo for much of the IL-1beta-dependent sterile inflammatory response. Furthermore, we find that cathepsin C, which controls the activity of a number of leukocyte serine proteases capable of processing IL-1beta, plays a major role in this caspase-1-independent pathway. Mice that are deficient in cathepsin C have reduced inflammatory responses to dying cells and silica crystals. In the absence of cathepsin C, caspase-1 becomes rate limiting such that mice doubly deficient in both of these proteases make little IL-1beta in vivo and have markedly attenuated inflammatory responses to the sterile stimuli. In contrast, these mutant mice generate normal inflammation in response to exogenous IL-1beta, indicating that cathepsin C and caspase-1 function upstream of IL-1beta, and, in their absence, all components of the pathway downstream of mature IL-1beta are intact. |
