TY - JOUR
T1 - Porphyromonas gingivalis infection enhances Th17 responses for development of atherosclerosis
AU - Cai, Yu
AU - Kobayashi, Ryoki
AU - Hashizume-Takizawa, Tomomi
AU - Kurita-Ochiai, Tomoko
PY - 2014/11
Y1 - 2014/11
N2 - Objectives Porphyromonas gingivalis has been shown to associate with the development of atherosclerosis. Recent studies indicate that IL-17-producing T helper 17 (Th17) cells have been correlated with the emergence of atherosclerosis. Therefore, we investigated whether the Th17 cell response and expression of Th17-related molecules, in contrast with Th1- and Treg cells, are enhanced by P. gingivalis-challenge in Apolipoprotein E knockout (ApoE KO) mice. Design Five mice were intravenously injected with P. gingivalis three times a week for 3 weeks and killed at 15 weeks of age. The proximal aorta lesion area, flow cytometry analysis and IL-17, IL-10, IFN-γ, and IL-1β levels in splenic cultures, and expression of Th17-related molecules in spleen and hearts were examined. Results P. gingivalis-challenge showed notable accumulation of atherosclerotic plaques by Oil Red O-staining in ApoE KO mice. Intracellular cytokine staining revealed that significantly elevated CD4+ interleukin (IL)-17A+ T cells and slightly increased CD4+ Foxp3+ T cells was recognized in spleen cells of P. gingivalis-challenged mice compared with those from non-infected mice. P. gingivalis-challenge significantly increased IL-17 and IL-1β production and RORγt expression in splenic cells. Furthermore, the expression of Th17-related genes such as IL-6, TGF-β, RORγt and STAT3 were elevated in splenic cells as well as heart tissue of P. gingivalis-challenged mice. Conclusion These results suggest that P. gingivalis infection may enhance pro-inflammatory Th17 cell responses in lesion areas and spleen, thereby accelerating atherosclerosis.
AB - Objectives Porphyromonas gingivalis has been shown to associate with the development of atherosclerosis. Recent studies indicate that IL-17-producing T helper 17 (Th17) cells have been correlated with the emergence of atherosclerosis. Therefore, we investigated whether the Th17 cell response and expression of Th17-related molecules, in contrast with Th1- and Treg cells, are enhanced by P. gingivalis-challenge in Apolipoprotein E knockout (ApoE KO) mice. Design Five mice were intravenously injected with P. gingivalis three times a week for 3 weeks and killed at 15 weeks of age. The proximal aorta lesion area, flow cytometry analysis and IL-17, IL-10, IFN-γ, and IL-1β levels in splenic cultures, and expression of Th17-related molecules in spleen and hearts were examined. Results P. gingivalis-challenge showed notable accumulation of atherosclerotic plaques by Oil Red O-staining in ApoE KO mice. Intracellular cytokine staining revealed that significantly elevated CD4+ interleukin (IL)-17A+ T cells and slightly increased CD4+ Foxp3+ T cells was recognized in spleen cells of P. gingivalis-challenged mice compared with those from non-infected mice. P. gingivalis-challenge significantly increased IL-17 and IL-1β production and RORγt expression in splenic cells. Furthermore, the expression of Th17-related genes such as IL-6, TGF-β, RORγt and STAT3 were elevated in splenic cells as well as heart tissue of P. gingivalis-challenged mice. Conclusion These results suggest that P. gingivalis infection may enhance pro-inflammatory Th17 cell responses in lesion areas and spleen, thereby accelerating atherosclerosis.
KW - Atherosclerosis
KW - Porphyromonas gingivalis
KW - Regulatory T cells
KW - T-helper 1 cells
KW - T-helper 17 cells
UR - http://www.scopus.com/inward/record.url?scp=84905693976&partnerID=8YFLogxK
U2 - 10.1016/j.archoralbio.2014.07.012
DO - 10.1016/j.archoralbio.2014.07.012
M3 - Article
C2 - 25103543
AN - SCOPUS:84905693976
SN - 0003-9969
VL - 59
SP - 1183
EP - 1191
JO - Archives of Oral Biology
JF - Archives of Oral Biology
IS - 11
ER -