Porphyromonas gingivalis induces myocarditis and/or myocardial infarction in mice and IL-17A is involved in pathogenesis of these diseases

• Published in: Archives of oral biology 2011-11, Vol.56 (11), p.1290-1298
• Main Authors: Akamatsu, Yuki, Yamamoto, Toshiro, Yamamoto, Kenta, Oseko, Fumishige, Kanamura, Narisato, Imanishi, Jiro, Kita, Masakazu
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Bacteremia; Bacteremia - microbiology; Cardiovascular diseases; Colony-forming cells; Dentistry; Gene expression; Heart diseases; IL-17A; Inflammation; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Interleukin 1; Interleukin 18; Interleukin 6; Interleukin-17 - biosynthesis; Interleukin-17 - genetics; Interleukin-17 - physiology; Leukocytes (neutrophilic); Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes; Myocardial infarction; Myocardial Infarction - microbiology; Myocarditis; Myocarditis - microbiology; Myocardium - metabolism; Pathogenesis; Periodontitis; Porphyromonas gingivalis; Porphyromonas gingivalis - pathogenicity; Real-Time Polymerase Chain Reaction; Specific Pathogen-Free Organisms; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0003-9969; 1879-1506
• DOI: 10.1016/j.archoralbio.2011.05.012

Abstract Objectives Although an association between periodontitis and cardiovascular diseases has been suggested, the role of Porphyromonas gingivalis in cardiovascular diseases is not clear. In this study, we examined whether experimental bacteremia of P. gingivalis causes cardiovascular diseases and investigated the mechanism of pathogenesis of cardiovascular diseases induced by P. gingivalis. Design C57BL/6 mice were intravenously inoculated with 2.0 × 108 CFU of P. gingivalis A7436 strain. Mice were sacrificed at specified days and their hearts were collected. The collected organs were divided into two halves and used for histological evaluation and cytokine analysis. IL-17A−/− , IFN-γ−/− and TNF-α−/− mice were also intravenously inoculated and the histological changes of hearts in mice were examined. Results Myocarditis and/or myocardial infarction were observed in mice injected with P. gingivalis . The levels of IL1-β, IL-6, IL-17A, IL-18, TNF-α and IFN-γ mRNA increased significantly after P. gingivalis injection. In particular, high levels of IL-17A and IFN-γ mRNA expression were observed in hearts of mice after P. gingivalis injection in comparison with these levels before injection. Furthermore, the production of IL-17A was detected in hearts of wild-type mice after P. gingivalis injection. In wild-type, TNF-α−/− and IFN-γ−/− mice, moderate infiltration of neutrophils and monocytes was observed in hearts at 5 days after injection. In contrast, no inflammatory findings were observed in hearts of IL-17A−/− mice. Conclusion We have demonstrated that an experimental bacteremia of P. gingivalis could induce myocarditis and/or myocardial infarction in mice, and IL-17A plays an important role in the pathogenesis of these diseases.