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J Immunol. 2008 Dec 15;181(12):8194-8.

Cutting edge: critical role for mesothelial cells in necrosis-induced inflammation through the recognition of IL-1 alpha released from dying cells.

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  • 1Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.


Endogenous danger signals released from necrotic cells are thought to be sensed by phagocytes leading to secretion of IL-1alpha and neutrophilic recruitment. However, the mechanisms for IL-1alpha production and IL-1alpha-mediated sterile inflammation remain poorly understood. We report here that necrotic cell extracts elicited little secretion of CXCL1 and IL-6 from macrophages but robust production in mesothelial cells. The induction of CXCL1 as well as activation of NF-kappaB and MAPKs by cytosolic extracts required the presence of IL-1alpha in the necrotic cell. Conversely, expression of IL-1R and MyD88 but not IL-1alpha, RICK, TLR2, TLR4, TRIF, or inflammasome components in mesothelial cells was critical for the production of CXCL1. Furthermore, IL-1alpha was critical to induce the recruitment of neutrophils in the peritoneal cavity via CXCR2. These studies show that IL-1alpha is a key danger signal released from necrotic cells to trigger CXCL1 secretion and recruitment of neutrophils via IL-1R/MyD88 on neighboring mesothelial cells.

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