Spliceosome-associated protein 130 exacerbates alcohol-induced liver injury by inducing NLRP3 inflammasome-mediated IL1 β in mice.

Spliceosome-associated protein 130 exacerbates alcohol-induced liver injury by inducing NLRP3 inflammasome-mediated IL1β in mice. Am J Pathol. 2018 Jan 16;: Authors: Kim JW, Roh YS, Jeong H, Yi HK, Lee MH, Lim CW, Kim B Abstract Excessive alcohol consumption leads to chronic liver diseases. Macrophage-inducible C-type lectin (Mincle) is a C-type lectin receptor that recognizes spliceosome-associated protein 130 (SAP130) known as an endogenous ligand released from dying cells. Our aim was to examine the role of Mincle-SAP130 in the pathogenesis of alcoholic liver disease. Alcohol-induced liver injury was induced in wild-type (WT) and Mincle knout-out (KO) mice using a chronic-binge ethanol-feeding model. Mincle KO mice showed significant lower hepatic steatosis, inflammation with neutrophil infiltration, and fibrosis compared to WT mice after alcohol feeding. In contrast, Mincle activation exacerbated alcohol-induced liver injury. Kupffer cells (KCs) are major sources of Mincle. IL1β expression was significantly down-regulated in Mincle KO mice compared to that in WT mice after alcohol consumption. Interestingly, expression and production of IL1β were significantly decreased in SAP130-treated KCs isolated from leucine-rich-containing family pyrin domain containing-3 (NLRP3) deficient mice compared to those in WT-KCs. Such results were also observed in cells treated with SAP130 plus Syk inhibitor. Furthermore, infiltration of invari...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research