title: Porphyromonas gingivalis infection enhances Th17 responses for development of atherosclerosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These results suggest that P. gingivalis infection may enhance pro-inflammatory Th17 cell responses in lesion areas and spleen, thereby accelerating atherosclerosis.
authors.affiliation: Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Sakaecho-nishi 2-870-1, Matsudo, Chiba 271-8587, Japan; Department of Periodontology, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Sakaecho-nishi 2-870-1, Matsudo, Chiba 271-8587, Japan.
authors.forename: Ryoki
authors.initials: R
authors.lastname: Kobayashi
authors.affiliation: Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Sakaecho-nishi 2-870-1, Matsudo, Chiba 271-8587, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hashizume-Takizawa
authors.affiliation: Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Sakaecho-nishi 2-870-1, Matsudo, Chiba 271-8587, Japan. Electronic address: ochiai.tomoko@nihon-u.ac.jp.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurita-Ochiai
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D018417:Th1 Cells / Q000473:pathology; D058504:Th17 Cells / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015415:Biomarkers; D020381:Interleukin-17; D053583:Interleukin-1beta; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: Atherosclerosis; Porphyromonas gingivalis; Regulatory T cells; T-helper 1 cells; T-helper 17 cells