Palmitic acid is a potent inducer of interleukin-6 gene expression in human coronary artery endothelial and smooth muscle cells

Plasma concentrations of free fatty acids (FFA) are markedly elevated in most cases of obesity. Dyslipidemia and obesity furthermore associate with chronic inflammation. We therefore asked whether FFA contribute to vascular inflammation by stimulating the expression of the inflammatory cytokine interleukin (IL)-6 in coronary artery cells.

To this end, we treated human coronary artery endothelial cells (CAEC) and smooth muscle cells (CASMC) with palmitic acid (C16:0), linoleic acid (C18:2 ((omega))6), IL-1β, and tumour necrosis factor (TNF)-α for 20 hours. Thereafter, IL-6, IL-6 receptor, and gp130 mRNA expression was quantified by real-time RT-PCR.

Both cell types expressed very low levels of IL-6 receptor mRNA. The mRNA signals of IL-6 and gp130, however, were readily detectable. Whereas gp130 mRNA levels remained unchanged by FFA treatment, palmitic acid, but not linoleic acid, induced a 18-fold increase of IL-6 mRNA expression in CAEC (N=3, p<0.001) and a 7.5-fold increase in CASMC (N=3, p<0.01). These increases were found to be concentration-dependent reaching significance at a palmitic acid concentration of 0.25 mM. When compared with IL-1â and TNF-α, palmitic acid furthermore turned out to be a very potent stimulus of IL-6 mRNA expression in human CAEC and CASMC.

In summary, we show here that palmitic acid, one of the most common FFA in the circulation, induces high levels of IL-6 mRNA expression in coronary artery cells. This finding points to an important contribution of this FFA to endothelial activation and vascular inflammation.