Clarithromycin attenuates the expression of monocyte chemoattractant protein-1 by activating toll-like receptor 4 in human mesangial cells
Clarithromycin attenuates the expression of monocyte chemoattractant protein-1 by activating toll-like receptor 4 in human mesangial cells
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DOI：
10.1007/s10157-016-1333-1
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发表时间：
2017-08
影响因子：
2.3
通讯作者：
K. Tsugawa;T. Imaizumi;Shojiro Watanabe;K. Tsuruga;H. Yoshida;Hiroshi Tanaka
中科院分区：
文献类型：
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作者：
K. Tsugawa;T. Imaizumi;Shojiro Watanabe;K. Tsuruga;H. Yoshida;Hiroshi Tanaka
背景肾脏Toll样受体4(Toll-like Receptor 4，TLR4)激活所诱导的信号传导通路在慢性肾脏疾病(CKD)中起着关键作用。最近的一些研究表明，克拉霉素(CAM)是一种14元环大环内酯类化合物，它通过抑制促炎趋化因子发挥肾脏保护作用。然而，其通过激活肾脏TLR4对信号转导通路的有益影响尚不清楚。用定量RT-PCR和酶联免疫吸附试验检测单核细胞趋化蛋白-1(MCP-1/CCL2)和白介素8(IL-8/CXCL8)的表达。用免疫印迹法检测核因子-κB(NF-κB)和p38丝裂原活化蛋白激酶(MAPK)的活性。结果在不损伤细胞的情况下，CAM可抑制MCP-1mRNA和蛋白的表达，但不影响IL-8的表达。结论：CAM通过抑制p38MAPK活性和减少MCP-1的表达而发挥肾保护作用，其作用机制可能与抑制p38MAPK活性有关，但不影响NF-κB的活性。鉴于TLR4信号在CKD中的意义，CAM可能是治疗CKD的潜在选择。
BackgroundSignaling pathways induced by the activation of renal toll-like receptor 4 (TLR4) play a pivotal role in chronic kidney disease (CKD). Some recent studies suggested that clarithromycin (CAM), a 14-membered ring macrolide, exerts renoprotective effects by suppressing proinflammatory chemokines. However, its beneficial effects on signaling pathways through renal TLR4 activation are unknown.MethodsCultured human mesangial cells (MCs) were treated with lipopolysaccharide (LPS). Expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleukin-8 (IL-8/CXCL8) was analyzed by quantitative RT-PCR and enzyme-linked immunosorbent assay. Signaling pathways affected by CAM were determined by examining the activation of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) by performing western blotting.ResultsCAM inhibited both the mRNA and protein expression of MCP-1 without cell injury but did not affect those expressions of IL-8 in LPS-stimulated MCs. Interestingly, CAM decreased p38 MAPK activation by inhibiting phosphorylation but did not affect NF-κB activation.ConclusionOur results indicated that CAM exerted renoprotective effects by suppression of p38 MAPK activity and by decreasing the expression of MCP-1 in LPS-stimulated MCs. Given the implication of TLR4 signaling in CKD, CAM may be a potential treatment of choice for CKD.