A Benzenediamine Analog FC-99 Drives M2 Macrophage Polarization and Alleviates Lipopolysaccharide- (LPS-) Induced Liver Injury

Macrophages have variable functional phenotypes, high diversity, and plasticity and are involved in the pathogenesis of sepsis-induced liver injury. Alteration of macrophage polarization through activated (M1) macrophage to alternatively activated (M2) macrophage has emerged as a potential therapeut...

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Bibliographic Details
Main Authors: Wei Gong, Haiyan Zhu, Li Lu, Yayi Hou, Huan Dou
Format: Article
Language:English
Published: Hindawi Limited 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/7823069
Description
Summary:Macrophages have variable functional phenotypes, high diversity, and plasticity and are involved in the pathogenesis of sepsis-induced liver injury. Alteration of macrophage polarization through activated (M1) macrophage to alternatively activated (M2) macrophage has emerged as a potential therapeutic strategy. This study was designed to explore the effect of a benzenediamine analog FC-99 on macrophage polarization in vitro and lipopolysaccharide- (LPS-) induced liver injury followed by the underlying mechanisms. For in vitro experiments, FC-99 inhibited M1-related macrophage factors and promoted M2-related markers induced by IL-4 in the mouse macrophage cell line RAW264.7. Moreover, FC-99-induced macrophages polarized to M2 phenotype which could be repressed by a PPAR-γ inhibitor but not STAT6 siRNA knockdown, indicating FC-99-induced M2 macrophage polarization through PPAR-γ rather than STAT6 signal. In LPS-induced septic mice, FC-99 pretreated mice displayed lower expression of M1 markers together with the increased M2 marker CD206 and improvement of liver injury. These findings illustrated that FC-99 could promote M2 macrophage polarization via PPAR-γ signaling and seemed to be a potential therapeutic candidate for inflammatory liver injury.
ISSN:0962-9351
1466-1861