Molecular mechanism underlying the inflammatory complication of leptin in macrophages
Molecular mechanism underlying the inflammatory complication of leptin in macrophages
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DOI：
10.1016/j.molimm.2010.06.006
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发表时间：
2010-09-01
影响因子：
3.6
通讯作者：
Li, Liwu
中科院分区：
文献类型：
--
作者：
Vaughan, Tamisha;Li, Liwu
瘦素是一种参与调节食物摄入和体重的关键脂肪因子，最近被发现与炎症加剧有关。血液循环中瘦素水平升高与患有心血管并发症的肥胖个体炎症增加相关。然而，其潜在的分子机制尚不清楚。在本报告中，我们证明瘦素单独不能诱导小鼠巨噬细胞和人单核细胞中诸如白细胞介素 - 6（IL - 6）等炎症细胞因子的表达。相反，瘦素显著增强脂多糖（LPS）诱导IL - 6表达的作用。关键的炎症信号分子白细胞介素 - 受体相关激酶1（IRAK - 1）部分参与介导LPS和瘦素的作用。IRAK - 1缺陷型巨噬细胞在LPS或LPS加瘦素刺激后，IL - 6的表达显著降低。从机制上讲，我们观察到瘦素增加人单核细胞和小鼠巨噬细胞中IRAK - 1的表达。综上所述，我们的数据表明，在肥胖相关炎症的发病机制中，瘦素主要作为炎症的辅助因子而非引发因子。（C）2010爱思唯尔有限公司。保留所有权利。
Leptin a key adipokine involved in regulating food Intake and body weight has been recently implicated in the exacerbation of inflammation Elevated leptin levels in blood circulation are correlated with increased inflammation in obese individuals with cardiovascular complications However the underlying molecular mechanism is poorly understood In this report we demonstrated that leptin alone failed to induce the expression of inflammatory cytokines such as IL-6 in murine macrophages and human monocytic cells Instead leptin significantly augment the effect of LPS in inducing the expression of IL-6 The key Inflammatory signaling molecule Interleukin-Receptor Associate Kinase 1 (IRAK-1) is partially involved in mediating the effects of both LPS and leptin IRAK-1 deficient macrophages exhibit significantly lower expression of IL-6 following LPS or LPS plus leptin stimulation Mechanistically we observed that leptin increases the expression of IRAK-1 in both human monocytes and murine macrophages Taken together our data reveal that leptin primarily serves as a helper instead of an initiator of inflammation during the pathogenesis of obesity-related inflammation (C) 2010 Elsevier Ltd All rights reserved