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Interleukin 6 Augments Mechanical Strain-Induced C-reactive Protein Synthesis via the Stretch-Activated Channel-Nuclear Factor κ B Signal Pathway

Interleukin 6 Augments Mechanical Strain-Induced C-reactive Protein Synthesis via the Stretch-Activated Channel-Nuclear Factor κ B Signal Pathway

Huaineng Zhou, Yanhui Li, Genya Huang, Xingyuan Gu, Jianping Zeng, Yi Li, Chufan Luo, Baiqin Ou, Yi Zhang, Zhongkai Wu, Lilong Tang

Heart. 2013 Apr;99(8):570-6.

PMID: 23257175

Abstract:

Objectives:
C-reactive protein (CRP), an inflammation marker, is a strong independent risk factor for cardiovascular disease. Vessels are able to express CRP; however, the molecular mechanism behind this expression is not clear.
Methods:
Reverse transcription PCR and ELISA were used to detect messenger RNA and proteins of CRP and nuclear factor κB (NF-κB) activity in vessel rings stretched with different mechanical strains.
Results:
Interleukin (IL)-6 treatment did not induce CRP expression in vessel rings of white rabbits in the absence of mechanical strain. In contrast, IL-6 augmented CRP expression in vessel rings stretched with mechanical strains of 3 and 5 g (CRP mRNA, IL-6: 11.367±1.68 and 12.78±0.76 vs vehicle: 7.27±0.88 and 8.3±0.91 folds, respectively; CRP, IL-6: 12.79±1.62 and 14.05±2.1 vs vehicle: 7.72±1.04 and 8.16±1.52 folds, respectively; p<0.05 vs 0 g group and vehicle control group; n=5), and this effect was completely blocked by treatment with gadolinium III chloride hexahydrate (GdCl3). Moreover, IL-6 treatment increased NF-κB activity in vessels stretched with a mechanical strain of 3 g, and this effect was blocked by stretch-activated channel inhibitors (streptomycin or GdCl3) and the NF-κB peptide inhibitor SN50, but not by the inactive SN50 analogue SN50M. We also performed similar experiments on human internal mammary arteries and obtained similar results.
Conclusions:
These results indicate that the inflammatory cytokine IL-6 alone does not induce CRP synthesis in vessels in the absence of mechanical strain; however, IL-6 augments mechanical strain-induced CRP synthesis in vessels via the stretch-activated channel-NF-κB pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP13450845	Gadolinium(III) chloride hexahydrate		13450-84-5	Price

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