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Cutting Edge: Critical Role for Mesothelial Cells in Necrosis-Induced Inflammation through the Recognition of IL-1α Released from Dying Cells

2008; American Association of Immunologists; Volume: 181; Issue: 12 Linguagem: Inglês

10.4049/jimmunol.181.12.8194

1550-6606

Tatjana Eigenbrod, Jong‐Hwan Park, Jürgen Harder, Yoichiro Iwakura, Gabriel Núñez,

Inflammasome and immune disorders

Abstract Endogenous danger signals released from necrotic cells are thought to be sensed by phagocytes leading to secretion of IL-1α and neutrophilic recruitment. However, the mechanisms for IL-1α production and IL-1α-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-κB and MAPKs by cytosolic extracts required the presence of IL-1α in the necrotic cell. Conversely, expression of IL-1R and MyD88 but not IL-1α, RICK, TLR2, TLR4, TRIF, or inflammasome components in mesothelial cells was critical for the production of CXCL1. Furthermore, IL-1α was critical to induce the recruitment of neutrophils in the peritoneal cavity via CXCR2. These studies show that IL-1α 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.