Koji Tsugawa1, Tadaatsu Imaizumi2, Shojiro Watanabe1, Kazushi Tsuruga1, Hidemi Yoshida2, Hiroshi Tanaka3,4. 1. Department of Pediatrics, Hirosaki University Hospital, Hirosaki University, Hirosaki, 036-8563, Japan. 2. Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki University, Hirosaki, 036-8562, Japan. 3. Department of Pediatrics, Hirosaki University Hospital, Hirosaki University, Hirosaki, 036-8563, Japan. hirotana@hirosaki-u.ac.jp. 4. Department of School Health Science, Faculty of Education, Hirosaki University, Hirosaki, 036-8560, Japan. hirotana@hirosaki-u.ac.jp.
Abstract
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-κB (NF-κB) 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-κB 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.
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-κB (NF-κB) 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-κB 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.
Authors: Julia Lepenies; Kevin S Eardley; Tina Kienitz; Martin Hewison; Thomas Ihl; Paul M Stewart; Paul Cockwell; Marcus Quinkler Journal: Nephron Clin Pract Date: 2011-06-15
Authors: Marian Kacerovsky; Roberto Romero; Martin Stepan; Jaroslav Stranik; Jan Maly; Lenka Pliskova; Radka Bolehovska; Vladimir Palicka; Helena Zemlickova; Helena Hornychova; Jiri Spacek; Bo Jacobsson; Percy Pacora; Ivana Musilova Journal: Am J Obstet Gynecol Date: 2020-07 Impact factor: 10.693