BET protein inhibitor apabetalone represses Porphyromonas gingivalis LPS-induced macrophage M1 polarization via regulating miR-130a/STAT3 axis

Periodontitis is a frequent chronic inflammatory disorder destroying periodontium.Recent studies have revealed the role of bromodomain and extraterminal domain inhibitor(BETi)and microRNA(miR)-130a in regulating macrophage polarization and pro-inflammatory response.However,little is known about whether apabetalone(a novel BETi)and miR-130a are correlated with chronic inflammatory state in periodontitis by regulating macrophage polarization.Here murine RAW264.7 macrophages were applied as an in vitro inflammatory model.After treatment with Porphyromonas gingivalis-derived lipopolysaccharide(Pg LPS)and apabetalone,the expression of macrophage M1 polarization markers and inflammatory cytokines was assessed using real-time PCR,western blot,and enzyme-linked immuno sorbent assay(ELISA).MiR-130a level was assessed using real-time PCR,and the target gene was identified using dual luciferase reporter assay.We demonstrated that apabetalone repressed Pg LPS-induced macrophage M1 polarization in a dose-dependent manner,as evidenced by decreased expression of inducible nitric oxide synthase(iNOS),CD86,and pro-inflammatory cytokines,and increased expression of Arg-1 and CD206.Mechanistically,Pg LPS increased miR-130a expression in macrophages,whereas apabetalone treatment repressed the effect.Functionally,forced expression of miR-130a promoted macrophage M1 polarization,and signal transducer and activator of transcription(STAT)-3 was the direct target gene of miR-130a in the process.Taken together,apabetalone decreases Pg LPS-induced macrophage M1 polarization via regulating miR-130a-3p/STAT3 axis,and may be a promising target for the clinical management of periodontitis.