title: Uric acid induces renal inflammation via activating tubular NF-κB signaling pathway.
abstract: Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling.
authors: Center for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors: Yang
authors: Y
authors: Zhou
authors: Li
authors: L
authors: Fang
authors: Lei
authors: L
authors: Jiang
authors: Ping
authors: P
authors: Wen
authors: Hongdi
authors: H
authors: Cao
authors: Weichun
authors: W
authors: He
authors: Chunsun
authors: C
authors: Dai
authors: Junwei
authors: J
authors: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009393:Nephritis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism*
chemical_list: C491768:Ccl2 protein, mouse; C503460:Ccl5 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014527:Uric Acid