Macrophage Sphingosine 1-Phosphate Receptor 2 Blockade Attenuates Liver Inflammation and Fibrogenesis Triggered by NLRP3 Inflammasome.

Frontiers in Immunology
Lei HouLiying Li

Abstract

NLR family pyrin domain containing 3 (NLRP3) inflammasome accompanies chronic liver injury and is a critical mediator of inflammation-driven liver fibrosis. Sphingosine 1-phosphate (S1P)/S1P Receptor (S1PR) signaling participates in liver fibrogenesis by affecting bone marrow (BM)-derived monocytes/macrophage (BMM) activation. However, the relationship between S1P/S1PR signaling and NLRP3 inflammasome in BMMs remains unclear. Here, we found significantly elevated gene expression of NLRP3 inflammasome components (NLRP3, pro-interleukin-1β, and pro-interleukin-18) and the activation of NLRP3 inflammasome significantly elevated during murine chronic liver injury induced by a bile duct ligation operation, a methionine-choline-deficient and high-fat diet, or carbon tetrachloride intraperitoneal injection. Moreover, the increased expression of sphingosine kinase 1 (SphK1), the rate-limiting synthetic enzyme of S1P, was positively correlated with NLRP3 inflammasome components in both patients and mouse model livers. Flow cytometry analysis and immunofluorescence staining showed BMMs contributed to the significant proportion of NLRP3+ cells in murine inflammatory livers, but not Kupffer cells, dendritic cells, endothelial cells, T cell...Continue Reading

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Citations

Feb 27, 2021·Progress in Lipid Research·Stefano FiorucciMichele Biagioli
Apr 15, 2021·Cellular & Molecular Immunology·Seungwha PaikEun-Kyeong Jo
May 10, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Da ChengXin Ni
Aug 3, 2021·Trends in Immunology·Jonathan J LiangClare E Bryant
Aug 28, 2021·International Journal of Molecular Sciences·Islamy Rahma HutamiEiji Tanaka

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Methods Mentioned

BETA
biopsy
density gradient centrifugation
confocal microscopy
transfection
ELISA
FACS

Software Mentioned

Leica Qwin
Image
Pro Plus

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