Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC1

Title: Caspase-11 controls interleukin-1β release through degradation of TRPC1.

Authors: Bénédicte F Py, Mingzhi Jin, Bimal N Desai, Anirudh Penumaka, Hong Zhu, Maike Kober, Alexander Dietrich, Marta M Lipinski, Thomas Henry, David E Clapham, Junying Yuan

Journal, date & volume: Cell Rep, 2014 Mar 27 , 6, 1122-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24630989

Abstract
Caspase-11 is a highly inducible caspase that controls both inflammatory responses and cell death. Caspase-11 controls interleukin 1β (IL-1β) 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-1β without modulating caspase-1 cleavage or cell death in cultured macrophages. Consistently, trpc1(-/-) mice show higher IL-1β 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.