P53 Alleviates the Progression of Periodontitis by Reducing M1-type Macrophage Differentiation

AbstractOur objective is to explore the effect of P53 on the progression of periodontitis by regulating macrophages differentiation bothin vitro andin vivo. Eighteen normal and periodontitis gingival tissues were collected for detecting P53 expression and macrophages infiltration by immunofluorescence, real-time PCR (qPCR) and western-blot. The differentiation and the inflammatory cytokines (TNF- α and IL-6) expression of THP-1, RAW264.7 and bone marrow derived macrophage (BMDM) cells, treating with Pifithrin-α (P53 inhibitor) or Nutlin-3a (P53 activator) under lipopolysaccharide (LPS) stimulation, were observed by flow cytometry, qPCR and ELISA. The severity of periodontitis, inflammatory cytokines expression and macrophages infiltration were measured in experimental periodontitis wild-type mice andp53 gene conditional knocked-out (p53-CKO) mice, which were established by ligation and LPS injection. A higher number of P53-positive macrophages was found infiltrated in periodontitis tissues.In vitro experiments showed that compared with Nutlin-3a, the proportion of M1-type macrophages and the expression of TNF- α and IL-6 were higher in Pifithrin-α treated cells under LPS stimulation.In vivo experimental periodontitis mice, the Pifithrin- α intraperitoneal injection group showed greater alveolar bone loss, higher levels of TNF-α and IL-6 secretion and more M1-type macrophages infiltration, while the Nutlin-3a intraperitoneal injection group were observed mild symptoms co...
Source: Inflammation - Category: Allergy & Immunology Source Type: research