| First Author | Rühl S | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 10 | Pages | 2927-36 |
| PubMed ID | 26173909 | Mgi Jnum | J:233045 |
| Mgi Id | MGI:5780643 | Doi | 10.1002/eji.201545772 |
| Citation | Ruhl S, et al. (2015) Caspase-11 activates a canonical NLRP3 inflammasome by promoting K(+) efflux. Eur J Immunol 45(10):2927-36 |
| abstractText | Recognition of microbe-associated molecular patterns or endogenous danger signals by a subset of cytosolic PRRs results in the assembly of multiprotein signaling complexes, the so-called inflammasomes. Canonical inflammasomes are assembled by NOD-like receptor (NLR) or PYHIN family members and activate caspase-1, which promotes the induction of pyroptosis and the release of mature interleukin-1beta/-18. Recently, a noncanonical inflammasome pathway was discovered that results in caspase-11 activation in response to bacterial lipopolysaccharide (LPS) in the cytosol. Interestingly, caspase-11 induces pyroptosis by itself, but requires NLRP3, the inflammasome adapter ASC, and caspase-1 to promote cytokine secretion. Here, we have studied the mechanism by which caspase-11 controls IL-1beta secretion. Investigating NLRP3/ASC complex formation, we find that caspase-11 functions upstream of a canonical NLRP3 inflammasome. The activation of NLRP3 by caspase-11 during LPS transfection is a cell-intrinsic process and is independent of the release of danger signals. Furthermore, we show that active caspase-11 leads to a drop of intracellular potassium levels, which is necessary to activate NLRP3. Our study, therefore, sheds new light on the mechanism of noncanonical inflammasome signaling. |
