Pentamethoxyflavanone regulates macrophage polarization and ameliorates sepsis in mice.

Abstract

Macrophages, owning variable phenotypes and diverse functions, were becoming the target cells in inflammatory, infectious and autoimmune diseases. In the present study, we evaluated the effect of 5,7,3',4',5'-pentamethoxyflavanone (abbreviated as PMFA), a kind of flavonoid, on macrophage polarization, and investigated the underlying mechanism. We found that PMFA significantly inhibited M1 macrophage polarization and diminished the proinflammatory cytokines, meanwhile it greatly enhanced M2 macrophage related molecules. Moreover, PMFA facilitated the phenotype shift from M1 to M2. However, PMFA only slightly inhibited the activation of T and B cells. Further researches showed that the mechanisms can be attributed to PMFA's down-regulation on p-STAT1 and up-regulation on p-STAT6, the pivotal regulatory molecules for M1 and M2 polarization, respectively. In addition, PMFA ameliorated LPS- and cecal ligation and puncture (CLP)-induced sepsis in mice, as assessed by the raise of survival rate, descend of tissue damage and bronchoalveolar lavage fluid (BALF) cytokines. PMFA significantly decreased the expression of IL-1β, IL-6 and TNF-α and reduced the infiltration of M1 macrophages in lung. As expected, adoptive transfer of PMFA-pretreated M1 macrophages significantly increased survival rate of LPS-challenged mice compared with control mice. Taken together, the results indicate that PMFA regulates macrophage polarization via targeting the STAT1/STAT6 signals and its potential use in treatment of inflammatory disease.

• Authors: Lili Feng, Pingping Song, Hang Zhou, Ang Li, Yuxiang Ma, Xiong Zhang, Hailiang Liu, Ge Xu, Yang Zhou, Xuefeng Wu, Yan Shen, Yang Sun, Xudong Wu, Qiang Xu
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 89 Issue 1 Pg. 109-18 (May 01 2014) ISSN: 1873-2968 [Electronic] England
• PMID: 24607272 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• 5,7,3',4',5'-pentamethoxyflavanone
• Flavanones
• STAT1 Transcription Factor
• STAT6 Transcription Factor
• Stat1 protein, mouse
• Stat6 protein, mouse

Topics

• Animals
• Blotting, Western
• Bronchoalveolar Lavage Fluid
• Cell Line
• Female
• Flavanones (pharmacology)
• Flow Cytometry
• Macrophages (drug effects, metabolism)
• Mice
• Mice, Inbred C57BL
• Polymerase Chain Reaction
• STAT1 Transcription Factor (metabolism)
• STAT6 Transcription Factor (metabolism)
• Sepsis (drug therapy)