Spliceosome-Associated Protein 130 Exacerbates Alcohol-Induced Liver Injury by Inducing NLRP3 Inflammasome-Mediated IL-1β in Mice
| Autor: | Hyeneui Jeong, Min-Ho Lee, Yoon Seok Roh, Jong-Won Kim, Chae Woong Lim, Ho-Keun Yi, Bumseok Kim |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Alcoholic liver disease Inflammasomes Interleukin-1beta Syk Inflammation Pathology and Forensic Medicine Pathogenesis 03 medical and health sciences Fibrosis Internal medicine NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Syk Kinase Lectins C-Type Receptor Liver injury Mice Knockout Ethanol Chemistry Membrane Proteins Proteins Inflammasome medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology Liver Neutrophil Infiltration Disease Progression Natural Killer T-Cells medicine.symptom medicine.drug Signal Transduction |
| Zdroj: | The American journal of pathology. 188(4) |
| ISSN: | 1525-2191 |
| Popis: | 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. The 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 knockout (KO) mice by using a chronic-binge ethanol-feeding model. Mincle KO mice showed significant lower hepatic steatosis, inflammation with neutrophil infiltration, and fibrosis compared with WT mice after alcohol feeding. In contrast, Mincle activation exacerbated alcohol-induced liver injury. Kupffer cells (KCs) are major sources of Mincle. IL-1β expression was significantly down-regulated in Mincle KO mice compared with that in WT mice after alcohol consumption. Interestingly, expression and production of IL-1β were significantly decreased in SAP130-treated KCs isolated from leucine-rich–containing family pyrin domain containing-3–deficient mice compared with those in WT KCs. Such results were also observed in cells treated with SAP130 plus Syk inhibitor. Furthermore, infiltration of invariant natural killer T cells was decreased in livers of Mincle KO mice. Finally, inhibition of Syk signaling ameliorated alcohol-induced liver injury. Collectively, these results demonstrated that interaction between Mincle and SAP130 may promote the progression of alcoholic liver disease by IL-1β production in KCs and consequently increase inflammatory immune cell infiltration. |
| Databáze: | OpenAIRE |
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