Pentamethoxyflavanone regulates macrophage polarization and ameliorates sepsis in mice
Pentamethoxyflavanone regulates macrophage polarization and ameliorates sepsis in mice
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五甲氧基黄烷酮调节巨噬细胞极化并改善小鼠脓毒症
DOI：
10.1016/j.bcp.2014.02.016
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发表时间：
2014-05-01
影响因子：
5.8
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Peng, Lili;Song, Pingping;Xu, Qiang
巨噬细胞具有可变的表型和多样的功能，正逐渐成为炎症性、感染性及自身免疫性疾病的靶细胞。在本研究中，我们评估了一种类黄酮——5,7,3',4',5'-五甲氧基黄烷酮（简称为PMFA）对巨噬细胞极化的影响，并探究了其潜在机制。我们发现，PMFA显著抑制M1型巨噬细胞极化，减少促炎细胞因子，同时大幅增强与M2型巨噬细胞相关的分子。此外，PMFA促进巨噬细胞表型从M1型向M2型转变。然而，PMFA仅轻微抑制T细胞和B细胞的活化。进一步研究表明，其机制可归因于PMFA分别下调p-STAT1（M1型极化的关键调节分子）和上调p-STAT6（M2型极化的关键调节分子）。另外，通过生存率提高、组织损伤减轻以及支气管肺泡灌洗液（BALF）细胞因子水平下降来评估，PMFA改善了脂多糖（LPS）及盲肠结扎穿孔术（CLP）诱导的小鼠脓毒症。PMFA显著降低白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达，并减少M1型巨噬细胞在肺部的浸润。正如预期，与对照小鼠相比，过继转移经PMFA预处理的M1型巨噬细胞显著提高了LPS攻击小鼠的生存率。综上所述，研究结果表明PMFA通过靶向STAT1/STAT6信号通路调节巨噬细胞极化，在炎症性疾病的治疗中具有潜在应用价值。（C）2014爱思唯尔公司版权所有。
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-1 beta, IL-6 and TNF-alpha 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. (C) 2014 Elsevier Inc. All rights reserved.