All-Trans Retinoic Acid Modulates The Immune Status of M2 Macrophages in Experimental Periodontitis Induced by Porphyromonas Gingivalis in Mice

Abstract Background: M2 macrophages are important innate immune cells that participate in the pathogenesis of periodontitis. The effect of all-trans retinoic acid (ATRA) on the immune status of M2 macrophages in periodontitis has not been reported.Methods: An experimental model of periodontitis was established in mice by oral administration of Porphyromonas gingivalis, and then ATRA or vehicle was administered orally to model mice every other day (P.g+ATRA and P.g+CMC mice, respectively). Flow cytometry was used to analyze the numbers of F4/80+CD206+ M2 macrophages in the gingiva, spleen, and peritoneal lavage fluid (PLF). M2 macrophage–related cytokines were quantified by real-time reverse transcription-polymerase chain reaction.Results: Compared with P.g+CMC mice, P.g+ATRA mice showed a significantly reduced cemento-enamel junction to alveolar bone crest (CEJ-ABC) distance. The percentage of F4/80+CD206+ M2 macrophages in gingiva, PLF and spleen in model mice increased after ATRA treatment. The mRNA expression levels of M2 macrophage­–related cytokines (IL-10, TGF-b1 and Arg-1) in gingiva, PLF and spleen of P.g+ATRA mice were higher than those of P.g+CMC mice.Conclusions: These results suggested that ATRA modulates the immune status of M2 macrophages and provides protection against periodontitis by enhancing M2 activation.