Non-canonical Caspase-1 Signaling Drives RIP2-Dependent and TNF-α-Mediated Inflammation In Vivo
Sören Reinke, Mary Linge, Hans H. Diebner, Hella Luksch, Silke Glage, A Gocht, Avril A. B. Robertson, Matthew A. Cooper, Sigrun R. Hofmann, Ronald Naumann, Mihail Sarov, Rayk Behrendt, Axel Roers, Frank Peßler, Joachim Roesler, Angela Rösen‐Wolff, Stefan Winkler
Abstract
mice, caspase-1-C284A mice show pronounced hypothermia and increased levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and IL-6 when challenged with lipopolysaccharide (LPS). Caspase-1-C284A signaling is RIP2 dependent and mediated by TNF-α but independent of the NLRP3 inflammasome. LPS-stimulated whole blood from patients carrying loss-of-function missense mutations in CASP1 secretes higher amounts of TNF-α. Taken together, these results reveal non-canonical caspase-1 signaling in vivo.