Effect Of Histone Deacetylase Inhibitor On Inflammatory Response Of Alveolar Macrophages Induced By Lipopolysaccharide

Objective:Acute lung disease is characterized by inflammation.This research aimed to investigate effect of trichostatin A(TSA)on microRNA-146a(miR-146a)and tumor necrosis factor ?(TNF-?)in lipopolysaccharide(LPS)-induced alveolar macrophage injury model.Methods:Rat alveolar macrophage,NR8383,was cultured and induced using LPS to establish acute lung injury model in vitro level.TSA was administrated to LPS-induced NR8383 cells.The morphological changes of the cells were observed by invert phase contrast microscope.Quantitative reverse-transcription PCR(qRT-PCR)assay was utilized to evaluate TNF-? and miR-146 a mRNA expression in LPS and/or TSA treated NR8383 cells.Enzyme-link immunosorbent assay(ELISA)was used to examine TNF-? levels.ResuIts:1.This study selected 1 ng/ml and 10 ng/ml TSA as the optimal concentrations for treating NR8383 cells.LPS-induced acute lung injury model was successfully established.2.TSA administration significantly reduced levels of TNF-? and TNF-? mRNA in LPS-induced NR8383 cells compared to those in LPS-induced NR8383 cells(p<0.05).3.LPS induction significantly increased miR-146 a expression in NR8383 cells compared to NR8383 cells(p<0.05).TSA administration significantly enhanced miR-146 a expression in LPS-induced NR8383 cells compared to that in LPS-induced NR8383 cells(p<0.05).Conclusions:TSA administration exerted anti-inflammation functions in LPS-induced acute lung injury model in vitro,which might be triggered by inhibiting TNF-? molecule and up-regulating miR-146 a expression.The present data hint that TSA could be considered as a potential therapeutic agent for treating acute lung injury.