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Kidney Blood Press Res. 2012;35(4):211-9. doi: 10.1159/000332402. Epub 2012 Jan 3.

C-reactive protein induces interleukin-6 and thrombospondin-1 protein and mRNA expression through activation of nuclear factor-ĸB in HK-2 cells.

Author information

1
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China. wanghai2192@sina.com

Abstract

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 μg/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-κB) was studied via EMSA. A specific p38MAPK inhibitor (SB203580) and an NF-κB 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-β(1 )(TGF-β(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-β(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-κB-mediated signal transduction. SB203580 (5 μM) and PDTC (50 μM) 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-κB signaling pathways and TGF-β(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.

PMID:
22223149
DOI:
10.1159/000332402
[Indexed for MEDLINE]
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