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Cell Rep. 2014 Mar 27;6(6):1122-1128. doi: 10.1016/j.celrep.2014.02.015. Epub 2014 Mar 13.

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

Author information

1
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; International Center for Infectiology Research, INSERM U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Claude Bernard Lyon 1 University, 69007 Lyon, France.
2
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
3
Department of Cardiology, Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
4
Walther Straub Institute of Pharmacology and Toxicology, German Lung Center (DZL), Ludwig Maximilian University Munich, 80336 Munich, Germany.
5
International Center for Infectiology Research, INSERM U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Claude Bernard Lyon 1 University, 69007 Lyon, France.
6
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: junying_yuan@hms.harvard.edu.

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.

PMID:
24630989
PMCID:
PMC4239700
DOI:
10.1016/j.celrep.2014.02.015
[Indexed for MEDLINE]
Free PMC Article

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