Extracellular polysaccharide from Bordetella species reduces high glucose-induced macrophage apoptosis via regulating interaction between caveolin-1 and TLR4.
Extracellular polysaccharide from Bordetella species reduces high glucose-induced macrophage apoptosis via regulating interaction between caveolin-1 and TLR4.
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DOI：
10.1016/j.bbrc.2015.09.125
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发表时间：
2015-10
影响因子：
3.1
通讯作者：
Min Li;Fei Lin;Yanliang Lin;Wen Peng
中科院分区：
文献类型：
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作者：
Min Li;Fei Lin;Yanliang Lin;Wen Peng
微噬细胞凋亡是糖尿病患者动脉粥样硬化病变的关键事件。在本研究中，高糖处理抑制Akt磷酸化和激活caspase 3在原代腹腔巨噬细胞，导致细胞凋亡。缺氧延长高糖条件下巨噬细胞的存活。博氏杆菌胞外多糖（EPS）进一步减少细胞凋亡对高糖缺氧的反应。在高糖低氧条件下，EPS处理通过识别TLR 4促进小窝蛋白-1的磷酸化。Caveolin-1的磷酸化增加了细胞膜Glut 1的水平，促进了细胞对葡萄糖的消耗，这可能是EPS对高糖暴露的巨噬细胞具有保护作用的原因。进一步的研究表明，EPS诱导的依赖于TLR 4的caveolin-1磷酸化促进了caveolin-1与TLR 4的结合，这可能是激活TLR 4信号通路的关键。
Microphage apoptosis is a critical event in atherosclerotic lesions in patients with diabetes. In the present investigation, high glucose treatment inhibited Akt phosphorylation and activated caspase 3 in primary peritoneal macrophage, leading to cell apoptosis. Hypoxia prolonged macrophage survival in high glucose condition. Extracellular polysaccharide fromBordetellaspecies (EPS) further decreased cell apoptosis in response to high glucose during hypoxia. Under high glucose and hypoxic condition, EPS treatment promoted caveolin-1 phosphorylation by recognizing TLR4. Caveolin-1 phosphorylation elevated membrane Glut1 level to accelerate glucose consumption, which should be the reason for protective effect of EPS on macrophage exposed to high glucose. Further investigation demonstrated that TLR4-dependent caveolin-1 phosphorylation induced by EPS promoted association of caveolin-1 with TLR4, which should be critical for activation of TLR4 signaling pathway.