Journal
CLINICAL AND EXPERIMENTAL NEPHROLOGY
Volume 21, Issue 4, Pages 573-578Publisher
SPRINGER
DOI: 10.1007/s10157-016-1333-1
Keywords
Clarithromycin; Mesangial cells; Monocyte chemoattractant protein-1; Toll-like receptor 4
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Funding
- Japan Society for Promotion of Science (JSPS KAKENHI) [25461615]
- Grants-in-Aid for Scientific Research [17K09681, 16K10055] Funding Source: KAKEN
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Background Signaling 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. Methods Cultured 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-kappa B (NF-kappa B) and p38 mitogen-activated protein kinase (MAPK) by performing western blotting. Results CAM 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-kappa B activation. Conclusion Our 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.
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