PMID- 16131811 OWN - NLM STAT- MEDLINE DCOM- 20060420 LR - 20170118 IS - 1660-2129 (Electronic) IS - 1660-2129 (Linking) VI - 101 IP - 4 DP - 2005 TI - C-reactive protein induces NF-kappaB activation through intracellular calcium and ROS in human mesangial cells. PG - e165-72 AB - BACKGROUND: C-reactive protein (CRP) is known to have a direct proinflammatory effect in endothelial cells. However, little is known about the effect of CRP in intrinsic renal cells. We investigated the effects of CRP on the nuclear factor-kappaB (NF-kappaB) activation and monocyte chemoattractant protein-1 (MCP-1) gene expression in human mesangial cells and also examined whether intracellular calcium and reactive oxygen species (ROS) were involved in the CRP- induced NF-kappaB activation. METHODS: NF-kappaB binding activity and MCP-1 mRNA expression were measured by electrophoretic mobility shift assay and Northern blot analysis, respectively. Intracellular calcium was monitored by confocal microscopy using calcium sensitive dye, Fluo-3 and intracellular ROS production was determined, using 2',7'-dichlorofluorescin diacetate. RESULTS: CRP increased NF-kappaB binding activity in a dose-dependent manner (12.5-100 microg/ml), which was induced within 1 h after incubation and peaked around 3 h. CRP also increased the MCP-1 mRNA expression via activation of NF-kappaB. Both intracellular calcium and ROS was induced by CRP. Calcium chelator, BAPTA-AM and anti-oxidants such as N-acetylcysteine and tiron suppressed CRP-induced NF-kappaB activation. CONCLUSION: CRP exerted a proinflammatory effect in human mesangial cells by inducing MCP-1 gene expression via NF-kappaB activation, which was mediated, at least in part, through intracellular calcium and ROS. CI - Copyright 2005 S. Karger AG, Basel. FAU - Chang, Jai Won AU - Chang JW AD - Department of Internal Medicine, Urology, Asan Institute for Life Sciences, College of Medicine, University of Ulsan, Seoul, South Korea. FAU - Kim, Choung Soo AU - Kim CS FAU - Kim, Soon Bae AU - Kim SB FAU - Park, Su Kil AU - Park SK FAU - Park, Jung Sik AU - Park JS FAU - Lee, Sang Koo AU - Lee SK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050830 PL - Switzerland TA - Nephron Exp Nephrol JT - Nephron. Experimental nephrology JID - 101159770 RN - 0 (Antioxidants) RN - 0 (Chelating Agents) RN - 0 (Chemokine CCL2) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - 0 (Recombinant Proteins) RN - 139890-68-9 (1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester) RN - 4X87R5T106 (1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt) RN - 526U7A2651 (Egtazic Acid) RN - 9007-41-4 (C-Reactive Protein) RN - SY7Q814VUP (Calcium) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/pharmacology MH - Acetylcysteine/pharmacology MH - Antioxidants/pharmacology MH - Blotting, Northern MH - C-Reactive Protein/*pharmacology/*physiology MH - Calcium/*metabolism MH - Cells, Cultured MH - Chelating Agents/pharmacology MH - Chemokine CCL2/genetics/metabolism MH - Dose-Response Relationship, Drug MH - Egtazic Acid/analogs & derivatives/pharmacology MH - Electrophoretic Mobility Shift Assay MH - Gene Expression Regulation MH - Humans MH - Inflammation MH - Mesangial Cells/chemistry/drug effects/*metabolism MH - Microscopy, Confocal MH - NF-kappa B/genetics/*metabolism MH - RNA, Messenger/analysis/genetics MH - Reactive Oxygen Species/*metabolism MH - Recombinant Proteins/pharmacology MH - Time Factors EDAT- 2005/09/01 09:00 MHDA- 2006/04/21 09:00 CRDT- 2005/09/01 09:00 PHST- 2005/02/11 00:00 [received] PHST- 2005/05/25 00:00 [accepted] PHST- 2005/09/01 09:00 [pubmed] PHST- 2006/04/21 09:00 [medline] PHST- 2005/09/01 09:00 [entrez] AID - 87940 [pii] AID - 10.1159/000087940 [doi] PST - ppublish SO - Nephron Exp Nephrol. 2005;101(4):e165-72. doi: 10.1159/000087940. Epub 2005 Aug 30.