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(Apoe
shl)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 Apoe
shl 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 Apoe
shl 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.
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