Apolipoprotein CIII induces monocyte chemoattractant protein-1 and interleukin 6 expression via Toll-like receptor 2 pathway in mouse adipocytes.
Apolipoprotein CIII induces monocyte chemoattractant protein-1 and interleukin 6 expression via Toll-like receptor 2 pathway in mouse adipocytes.
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DOI：
10.1161/atvbaha.110.210427
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Yoshida M
中科院分区：
文献类型：
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作者：
Abe Y;Kawakami A;Osaka M;Uematsu S;Akira S;Shimokado K;Sacks FM;Yoshida M
研究载脂蛋白CIII（apoCIII）对肥胖、胰岛素抵抗或代谢综合征相关脂肪因子表达的直接影响。在肥胖、胰岛素抵抗或代谢综合征患者中，富含磷脂酰肌醇的脂蛋白中的ApoCIII升高。其水平也与促炎脂肪因子相关。将完全分化的小鼠3 T3 L1脂肪细胞与apoCIII孵育。ApoCIII激活3 T3 L1脂肪细胞的核因子κB，并诱导单核细胞趋化蛋白（MCP）1和白细胞介素（IL）6的表达。ApoCIII还激活细胞外信号调节激酶和p38。丝裂原活化蛋白激酶激酶（MEK）-1抑制剂PD 98059，而不是p38抑制剂SB 203580，抑制apoCIII诱导的MCP-1和IL-6上调。此前，研究表明apoCIII通过toll样受体（TLR）2激活促炎信号。TLR 2阻断抗体可阻断apoCIII诱导的核因子κB和细胞外信号调节激酶的活化，并抑制apoCIII诱导的MCP-1和IL-6的上调。ApoCIII还降低了3 T3 L1脂肪细胞的脂联素表达，这被TLR 2阻断抗体恢复。ApoCIII在TLR 2过表达的人胚肾293细胞中诱导MCP-1和IL-6的表达，但在没有TLR 2的野生型人胚肾293细胞中不诱导MCP-1和IL-6的表达。ApoCIII在野生型小鼠的白色脂肪组织中诱导MCP-1和IL-6的表达，并降低脂联素的表达，但在体内TLR 2缺陷小鼠中不诱导脂联素的表达。ApoCIII可能通过TLR 2激活细胞外信号调节激酶和核因子kB，并在体外和体内诱导促炎性脂肪因子的表达。因此，apoCIII将血脂异常与脂肪细胞中的炎症联系起来，而脂肪细胞中的炎症又可能导致动脉粥样硬化。
To examine the direct effect of apolipoprotein CIII (apoCIII) on adipokine expressions that are involved in obesity, insulin resistance, or metabolic syndrome. ApoCIII in triglyceride-rich lipoproteins is elevated in patients with obesity, insulin resistance, or metabolic syndrome. Its level is also associated with proinflammatory adipokines. Fully differentiated mouse 3T3L1 adipocytes were incubated with apoCIII. ApoCIII activated nuclear factor κB of 3T3L1 adipocytes and induced the expression of monocyte chemoattractant protein (MCP) 1 and interleukin (IL) 6. ApoCIII also activated extracellular signal–regulated kinase and p38. Mitogen-activated protein kinase kinase (MEK)-1 inhibitor PD98059, but not p38 inhibitor SB203580, inhibited apoCIII-induced upregulation of MCP-1 and IL-6. Previously, it was shown that apoCIII activates proinflammatory signals through toll-like receptor (TLR) 2. TLR2-blocking antibody abolished activation of nuclear factor κB and extracellular signal–regulated kinase induced by apoCIII and inhibited apoCIII-induced upregulation of MCP-1 and IL-6. ApoCIII also reduced adiponectin expression of 3T3L1 adipocytes, which was recovered by TLR2-blocking antibody. ApoCIII induced the expression of MCP-1 and IL-6 in TLR2-overexpressed human embryonic kidney 293 cells but not wild-type human embryonic kidney 293 cells without TLR2. ApoCIII induced the expression of MCP-1 and IL-6 and decreased adiponectin expression in white adipose tissue of wild-type mice but not of TLR2-deficient mice in vivo. ApoCIII may activate extracellular signal–regulated kinase and nuclear factor kB through TLR2 and induce proinflammatory adipokine expression in vitro and in vivo. Thus, apoCIII links dyslipidemia to inflammation in adipocytes, which, in turn, may contribute to atherosclerosis.