Atheroprotective nasal immunization with a heat shock protein 60 peptide from Porphyromonas gingivalis
주지영, 차길선, 김현주, 이주연, 최점일,
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주지영 ( Joo Ji-Young ) - Pusan National University School of Dentistry Department of Periodontology
차길선 ( Cha Gil-Sun ) - Pusan National University School of Dentistry Department of Periodontology
김현주 ( Kim Hyun-Joo ) - Pusan National University School of Dentistry Department of Periodontology
이주연 ( Lee Ju-Youn ) - Pusan National University School of Dentistry Department of Periodontology
최점일 ( Choi Jeom-Il ) - Pusan National University School of Dentistry Department of Periodontology
Abstract
Purpose: Immunization with Porphyromonas gingivalis heat shock protein 60 (PgHSP60) may have an immunoregulatory effect on atherogenesis. The aim of this study was to determine whether nasal immunization with a PgHSP60 peptide could reduce atherosclerotic plaque formation in apolipoprotein E knockout (ApoE KO) mice.
Methods: Seven-week-old male ApoE KO mice were assigned to receive a normal diet, a Western diet, a Western diet and challenge with PgHSP60-derived peptide 14 (Pep14) or peptide 19 (Pep19), or a Western diet and immunization with Pep14 or Pep19 before challenge with Pep14 or Pep19.
Results: Atherosclerotic plaques were significantly smaller in mice that received a Western diet with Pep14 nasal immunization than in mice that received a Western diet and no Pep14 immunization with or without Pep14 challenge. An immunoblot profile failed to detect serum reactivity to Pep14 in any of the study groups. Stimulation by either Pep14 or Pep19 strongly promoted the induction of CD4+CD25+forkhead box P3 (FoxP3)+ human regulatory T cells (Tregs) in vitro. However, the expression of mouse splenic CD4+CD25+FoxP3+ Tregs was lower in the Pep14-immunized mice than in the Pep14-challenged or Pep19-immunized mice. Levels of serum interferon gamma (IFN-γ) and transforming growth factor beta were higher and levels of interleukin (IL) 10 were lower in the Pep14-immunized mice than in the other groups. Induction of CD25? IL-17+ T helper 17 (Th17) cells was attenuated in the Pep14-immunized mice.
Conclusions: Nasal immunization with Pep14 may be a mechanism for attenuating atherogenesis by promoting the secretion of IFN-γ and/or suppressing Th17-mediated immunity.
키워드
Atherosclerosis; Cardiovascular diseases; Heat-shock proteins; Periodontitis; Porphyromonas gingivalis; Vaccines
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