Interleukin 6 augments mechanical strain-induced C-reactive protein synthesis via the stretch-activated channel-nuclear factor κ B signal pathway.

Abstract

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. 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. 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. 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.