RESUMO
Periodontitis is a prevalent oral inflammatory disease that leads to alveolar bone loss and may exert an adverse impact on systemic health. Periodontal disease may be associated with hepatocellular carcinoma (HCC); however, the mechanism of such an association is unknown. In this study, Stelic Animal model (STAM) mice, a model of nonalcoholic steatohepatitis (NASH)-HCC, were induced to develop periodontitis and subjected to histopathological and immunological analyses. HCC progression was greater in STAM mice with experimental periodontitis compared with that in STAM mice without experimental periodontitis. Tumor necrosis factor-α (TNFα), matrix metalloproteinase-9 (MMP9), collagen 1, and angiopoietin-like protein 2 (ANGPTL2) gene expression was significantly increased in the liver of the periodontitis group. ANGPTL2 was previously reported to be involved in the pathogenesis of periodontitis, and HCC and ANGPTL2 protein tended to be more abundant in the pocket epithelium of STAM mice with experimental periodontitis than in control STAM mice. ANGPTL2 levels in the serum of STAM mice with experimental periodontitis tended to be higher than in control STAM mice. Our results indicate that ANGPTL2 is produced in chronically inflamed periodontal tissue and then travels to the liver via the bloodstream where it accumulates to promote the progression of hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular , Modelos Animais de Doenças , Neoplasias Hepáticas , Periodontite , Animais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Periodontite/patologia , Periodontite/complicações , Periodontite/metabolismo , Camundongos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Proteínas Semelhantes a Angiopoietina/metabolismo , Proteínas Semelhantes a Angiopoietina/genética , Proteína 2 Semelhante a Angiopoietina , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fígado/patologia , Fígado/metabolismoRESUMO
BACKGROUND: We determined the effects and an accurate marker of periodontal treatment on serum interleukin (IL)-6 and high-sensitivity C-reactive protein (HsCRP) levels in systemically healthy individuals with periodontal disease. METHODS: This multicenter study included systemically healthy individuals with periodontal disease who received initial periodontal treatment and had no periodontal treatment history. Periodontal parameters, including periodontal inflamed surface area, masticatory efficiency, and periodontal disease classification; serum IL-6 and HsCRP levels; and serum immunoglobulin (Ig)G titers against periodontal pathogens were evaluated at baseline and after treatment. Subjects were classified as low or high responders (group) based on periodontal inflamed surface area changes. RESULTS: There were 153 participants. Only periodontal inflamed surface area changes were markedly different between low and high responders. Periodontal treatment (time point) decreased both serum IL-6 and HsCRP levels. The interaction between group and time point was remarkable only for serum IL-6 levels. Changes in serum immunoglobulin (Ig)G titers against periodontal pathogens were not associated with IL-6 changes in high responders. We analyzed the indirect effect of serum anti-Porphyromonas gingivalis type 2 IgG titer changes using mediation analysis and found no significance. However, the direct effect of group (low or high responder) on IL-6 changes was considerable. CONCLUSIONS: Periodontal treatment effectively decreased serum IL-6 levels, independent of periodontal pathogen infection, in systemically healthy individuals with periodontal disease.