RESUMO
Periodontitis, an oral inflammatory disease caused by periodontal pathogen infection, is the most prevalent chronic inflammatory disease and a major burden on healthcare. The TAM receptor tyrosine kinases (Tyro3, Axl and Mertk) and their ligands (Gas6 and Pros1) play a pivotal role in the resolution of inflammation and have been associated with chronic inflammatory and autoimmune diseases. In this study, we evaluated the effects of exogenous Pros1 in in vitro and in vivo models of periodontitis. We detected higher Pros1 but lower Tyro3 levels in inflamed gingival specimens of periodontitis patients compared with healthy controls. Moreover, Pros1 was mostly localized in the gingival epithelium of all specimens. In cultured human gingival epithelial cells (hGECs), Porphyromonas gingivalis LPS (p.g-LPS) stimulation down-regulated Pros1 and Tyro3. Exogenous Pros1 inhibited p.g-LPS-induced production of TNF-α, IL-6, IL-1ß, MMP9/2 and RANKL in a Tyro3-dependent manner as revealed by PCR, Western blot analysis, ELISA and gelatin zymography. Pros1 also restored Tyro3 expression down-regulated by p.g-LPS in hGECs. In rats treated with ligature and p.g-LPS, administration of Pros1 attenuated periodontitis-associated gingival inflammation and alveolar bone loss. Our mechanistic studies implicated SOCS1/3 and STAT1/3 as mediators of the in vitro and in vivo anti-inflammatory effects of Pros1. Collectively, the findings from this work supported Pros1 as a novel anti-inflammatory therapy for periodontitis.
Assuntos
Perda do Osso Alveolar/prevenção & controle , Proteínas de Ligação ao Cálcio/metabolismo , Periodontite/prevenção & controle , Substâncias Protetoras/administração & dosagem , Receptores Proteína Tirosina Quinases/metabolismo , Fator de Transcrição STAT1/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Adulto , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/patologia , Animais , Infecções por Bacteroidaceae/complicações , Infecções por Bacteroidaceae/microbiologia , Proteínas de Ligação ao Cálcio/administração & dosagem , Proteínas de Ligação ao Cálcio/genética , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Lipopolissacarídeos/toxicidade , Masculino , Pessoa de Meia-Idade , Periodontite/etiologia , Periodontite/patologia , Porphyromonas gingivalis/patogenicidade , Proteína S , Ratos , Ratos Sprague-Dawley , Receptores Proteína Tirosina Quinases/genética , Fator de Transcrição STAT1/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to investigate the clinical factors in relation to the cyclosporine A (CsA) induced gingival overgrowth (GO). STUDY DESIGN: Seventy-three participants were assigned as GO+ and GO-. Factors including demographic, pharmacological, gingival variables and the serum cyclophilin A (CyPA) concentration were analyzed. RESULTS: The occurrence of GO was 39.72%. Papillary bleeding index (PBI) had a significantly higher risk of GO than plaque index (PI), the ratio of CsA to CyPA, and serum CyPA concentration (odds ratio = 364.323, 25.791, 1.002, 0.096, respectively). The severity of GO correlated with PI, the ratio of CsA to CyPA, PBI, serum concentrations of CsA and CyPA (r = 0.366, 0.355, 0.344, 0.305, and -0.232, respectively). CONCLUSIONS: Since a cross-sectional study is not able to explain whether plaque and inflammation are the cause or consequence of GO, the ratio of CsA to CyPA may be a valuable marker for predicting GO.
