C-Reactive Protein Induces Interleukin-6 and Thrombospondin-1 Protein and mRNA Expression through Activation of Nuclear Factor-kappa B in HK-2 Cells

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	C-Reactive Protein Induces Interleukin-6 and Thrombospondin-1 Protein and mRNA Expression through Activation of Nuclear Factor-kappa B in HK-2 Cells
	Wang, Hai-rong 1; Chen, De-liang 1; Zhao, Mingming 1; Shu, Shao-wu 2; Xiong, Shi-xi 1; Gan, Xue-dong 1; Chao, Sheng-ping 1; Cao, Jian-lei 1
刊名	KIDNEY & BLOOD PRESSURE RESEARCH
	2012
卷号	35 期号:4 页码:211-219
关键词	C-reactive protein Renal tubular epithelial cells Mitogen-activated protein kinase Nuclear factor-kappa B Interleukin-6 Thrombospondin-1
ISSN号	1420-4096
通讯作者	Wang, HR (reprint author), Wuhan Univ, Zhongnan Hosp, Dept Cardiol, 169 Dong Hu Rd, Wuhan 430071, Peoples R China.
中文摘要	Background: Although C-reactive protein (CRP) is significantly increased in patients with diabetic nephropathy, whether CRP exerts direct proinflammatory effects on human renal tubular epithelial cells (HK-2 cells) is still unclear. Methods: HK-2 cells were incubated with purified CRP at clinically relevant concentrations (0, 5, 10, 20 and 40 mu g/ml). The protein and transcript levels of thrombospondin-1 (TSP-1) and interleukin-6 (IL-6) were determined by ELISA and RT-PCR. Phosphorylation of p38MAPK was investigated through Western blot analysis in HK-2 cells induced by CRP. The activation of nuclear factor-kappa B (NF-kappa B) was studied via EMSA. A specific p38MAPK inhibitor (SB203580) and an NF-kappa B inhibitor (PDTC; pyrrolidine dithiocarbamate) were used to analyze the signal transduction in CRP induction. To explore the direct or indirect role of CRP in HK-2 cells, IL-6 or TSP-1 antibodies were used. The expression of IL-6, TSP-1 and transforming growth factor-beta(1) (TGF-beta(1)) were determined through Western blot analysis in HK-2 cells. Results: In HK-2 cells, purified CRP significantly induced protein release and mRNA expression of IL-6 and TSP-1 in a dose- and time-dependent manner. TGF-beta(1) protein was overexpressed in HK-2 cells induced by CRP, which cannot be inhibited by IL-6 or TSP-1 antibodies. CRP triggered phosphorylation of p38MAPK and activation of NF-kappa B-mediated signal transduction. SB203580 (5 mu m) and PDTC (50 mu m) efficiently suppressed those effects of CRP in HK-2 cells. Conclusions: CRP induces IL-6 and TSP-1 protein release and mRNA expression from HK-2 cells via activation of the p38MAPK and NF-kappa B signaling pathways and TGE-beta(1) was highly expressed in HK-2 cells, suggesting that CRP plays an important role in the propagation and prolongation of inflammation in renal fibrosis. Copyright (C) 2012 S. Karger AG, Basel
英文摘要	Background: Although C-reactive protein (CRP) is significantly increased in patients with diabetic nephropathy, whether CRP exerts direct proinflammatory effects on human renal tubular epithelial cells (HK-2 cells) is still unclear. Methods: HK-2 cells were incubated with purified CRP at clinically relevant concentrations (0, 5, 10, 20 and 40 mu g/ml). The protein and transcript levels of thrombospondin-1 (TSP-1) and interleukin-6 (IL-6) were determined by ELISA and RT-PCR. Phosphorylation of p38MAPK was investigated through Western blot analysis in HK-2 cells induced by CRP. The activation of nuclear factor-kappa B (NF-kappa B) was studied via EMSA. A specific p38MAPK inhibitor (SB203580) and an NF-kappa B inhibitor (PDTC; pyrrolidine dithiocarbamate) were used to analyze the signal transduction in CRP induction. To explore the direct or indirect role of CRP in HK-2 cells, IL-6 or TSP-1 antibodies were used. The expression of IL-6, TSP-1 and transforming growth factor-beta(1) (TGF-beta(1)) were determined through Western blot analysis in HK-2 cells. Results: In HK-2 cells, purified CRP significantly induced protein release and mRNA expression of IL-6 and TSP-1 in a dose- and time-dependent manner. TGF-beta(1) protein was overexpressed in HK-2 cells induced by CRP, which cannot be inhibited by IL-6 or TSP-1 antibodies. CRP triggered phosphorylation of p38MAPK and activation of NF-kappa B-mediated signal transduction. SB203580 (5 mu m) and PDTC (50 mu m) efficiently suppressed those effects of CRP in HK-2 cells. Conclusions: CRP induces IL-6 and TSP-1 protein release and mRNA expression from HK-2 cells via activation of the p38MAPK and NF-kappa B signaling pathways and TGE-beta(1) was highly expressed in HK-2 cells, suggesting that CRP plays an important role in the propagation and prolongation of inflammation in renal fibrosis. Copyright (C) 2012 S. Karger AG, Basel
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Physiology ; Urology & Nephrology ; Peripheral Vascular Disease
研究领域[WOS]	Physiology ; Urology & Nephrology ; Cardiovascular System & Cardiology
关键词[WOS]	TUMOR-NECROSIS-FACTOR ; SMOOTH-MUSCLE-CELLS ; IN-VITRO ; CARDIOVASCULAR-DISEASE ; ENDOTHELIAL-CELLS ; TNF-ALPHA ; INFLAMMATION ; MACROPHAGES ; INHIBITION ; GAMMA
收录类别	SCI
资助信息	Hubei Province Scientific Research Foundation[2007AA301B36-3, 2009CDB059]; Hubei Province Health Department Important Foundation[JX2A19]; State Key Laboratory of Freshwater Ecology and Biotechnology[2010FB12]
语种	英语
WOS记录号	WOS:000303846100002
公开日期	2012-09-25
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/16961]
专题	水生生物研究所_鱼类生物学及渔业生物技术研究中心_期刊论文
作者单位	1.Wuhan Univ, Zhongnan Hosp, Dept Cardiol, Wuhan 430071, Peoples R China 2.State Key Lab Freshwater Ecol & Biotechnol, Wuhan, Peoples R China
推荐引用方式 GB/T 7714	Wang, Hai-rong,Chen, De-liang,Zhao, Mingming,et al. C-Reactive Protein Induces Interleukin-6 and Thrombospondin-1 Protein and mRNA Expression through Activation of Nuclear Factor-kappa B in HK-2 Cells[J]. KIDNEY & BLOOD PRESSURE RESEARCH,2012,35(4):211-219.
APA	Wang, Hai-rong.,Chen, De-liang.,Zhao, Mingming.,Shu, Shao-wu.,Xiong, Shi-xi.,...&Cao, Jian-lei.(2012).C-Reactive Protein Induces Interleukin-6 and Thrombospondin-1 Protein and mRNA Expression through Activation of Nuclear Factor-kappa B in HK-2 Cells.KIDNEY & BLOOD PRESSURE RESEARCH,35(4),211-219.
MLA	Wang, Hai-rong,et al."C-Reactive Protein Induces Interleukin-6 and Thrombospondin-1 Protein and mRNA Expression through Activation of Nuclear Factor-kappa B in HK-2 Cells".KIDNEY & BLOOD PRESSURE RESEARCH 35.4(2012):211-219.