| First Author | Py BF | Year | 2014 |
| Journal | Cell Rep | Volume | 6 |
| Issue | 6 | Pages | 1122-1128 |
| PubMed ID | 24630989 | Mgi Jnum | J:211710 |
| Mgi Id | MGI:5576076 | Doi | 10.1016/j.celrep.2014.02.015 |
| Citation | Py BF, et al. (2014) Caspase-11 controls interleukin-1beta release through degradation of TRPC1. Cell Rep 6(6):1122-8 |
| abstractText | Caspase-11 is a highly inducible caspase that controls both inflammatory responses and cell death. Caspase-11 controls interleukin 1beta (IL-1beta) secretion by potentiating caspase-1 activation and induces caspase-1-independent pyroptosis downstream of noncanonical NLRP3 inflammasome activators such as lipopolysaccharide (LPS) and Gram-negative bacteria. However, we still know very little about the downstream mechanism of caspase-11 in regulating inflammation because the known substrates of caspase-11 are only other caspases. Here, we identify the cationic channel subunit transient receptor potential channel 1 (TRPC1) as a substrate of caspase-11. TRPC1 deficiency increases the secretion of IL-1beta without modulating caspase-1 cleavage or cell death in cultured macrophages. Consistently, trpc1(-/-) mice show higher IL-1beta secretion in the sepsis model of intraperitoneal LPS injection. Altogether, our data suggest that caspase-11 modulates the cationic channel composition of the cell and thus regulates the unconventional secretion pathway in a manner independent of caspase-1. |
