Abstract
Recent studies have shown an association between periodontal disease and cardiovascular disease. We previously reported that Aggregatibacter actinomyctemcomitans（Aa）bacteremia accelerated atherosclerosis in apolipoprotein E-deficient spontaneously hyperlipidemic（Apoeshl）mice. Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. In this study, we investigated whether the functional imbalance between Th17, Th1, and regulatory T（Treg）cells, existed in Aa-challenged Apoeshl mice. The mice were intravenously treated with live Aa HK1651 or vehicles. Histomorphometric features of atheromatous lesions, IL-17+ CD4+, IFN-g+ CD4+, and Foxp3+CD4+ cell frequencies, serum IL-17, IL-6, TGF-β, IFN-γ, and IL-10 levels, and gene expression of Th17-related molecules were examined. Aa challenge induced a Th17/Th1 shift in Apoeshl mice. Aa-challenged splenic Th1 and Th17 cells greatly increased in contrast with reduction in Treg cells after their transient increase at 13 weeks. Serum cytokine levels of IL-6 were significantly enhanced during Aa-challenge. Similarly, gene expression of differentiation factors（IL-6, IL-17RA and IL-21）, growth/stabilization factor （IL-23）, and transcription factor（STAT3）involved in the development of Th17 cells, as well as Th1-related IFN-γ were also stimulated in Aa-challenged mice. These results suggest that Th17/Th1/Treg imbalance affect the progression of Aa- accelerated atherosclerosis.
