Py, Bénédicte F.Jin, MingzhiDesai, Bimal N.Penumaka, AnirudhZhu, HongKober, MaikeDietrich, AlexanderLipinski, Marta M.Henry, ThomasClapham, DavidYuan, Junying2015-04-012014Py, B. F., M. Jin, B. N. Desai, A. Penumaka, H. Zhu, M. Kober, A. Dietrich, et al. 2014. “Caspase-11 Controls Interleukin-1β Release through Degradation of TRPC1.” Cell reports 6 (6): 1122-1128. doi:10.1016/j.celrep.2014.02.015. http://dx.doi.org/10.1016/j.celrep.2014.02.015.2211-1247http://nrs.harvard.edu/urn-3:HUL.InstRepos:14351050SUMMARY 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.en-USJournal Article2015-04-0110.1016/j.celrep.2014.02.015