科研之友
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摘要
Th17 cells have been linked to the pathogenesis of several chronic inflammatory and autoimmune diseases. However, the role of Th17 cells and IL-17 in atherosclerosis remains poorly understood. We previously reported that Aggregatibacter actinomycetemcomitans (A alpha) bacteremia accelerated atherosclerosis accompanied by inflammation in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice. In this study, we investigated whether A alpha promotes the Th17 inducing pathway in A alpha-challenged Apoe(shl) mice. Mice were intravenously injected with live A alpha HK1651 or vehicles. Time-course analysis of splenic IL-17(+) CD4(+) cell frequencies, the proximal aorta lesion area, serum IL-17, IL-6, TGF-beta and IL-1 beta levels, the mRNA expression of Th17-related molecules such as IL-1 beta, IL-6, IL17RA, STAT3, IL-21, IL-23, TGF-beta and ROR gamma t, Th17-related microRNA levels and the levels of AIM-2, Mincle and NLRP3 were examined. Challenge with A alpha time dependently induced tropism of Th17 cells in the spleen and increase in atheromatous lesions in the aortic sinus of Apoe(shl) mice. Serum IL-17, IL-6, TGF-beta and IL-1 beta levels were significantly enhanced by A alpha. The gene expression of IL-1 beta, IL-6, IL-17RA, IL-21, IL-23, TGF-beta, STAT3, ROR gamma t, AIM-2, Mincle and NLRP3 was also time dependently stimulated in the aorta of A alpha-challenged mice. Furthermore, A alpha challenge significantly increased the expression of miR-146b and miR-155 in the aorta. Based on the results, it seems that A alpha stimulates Th17 induction that affects the progression of A alpha-accelerated atherosclerosis.
