HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury

HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury

Blog Article

Summary: Activated inflammation and pyroptosis in macrophage are closely associated with acute lung injury (ALI).Histone deacetylase 3 (HDAC3) serves as an important enzyme that could repress gene expression by mediating chromatin remodeling.In this study, we found that HDAC3 was highly expressed in lung tissues of lipopolysaccharide (LPS)-treated mice.Lung tissues from macrophage HDAC3-deficient mice stimulated with LPS Glucomannan Powder showed alleviative lung pathological injury and inflammatory response.HDAC3 silencing significantly blocked the activation of cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway in LPS-induced macrophage.

LPS could recruit HDAC3 and H3K9Ac to bbs-dog-collar- the miR-4767 gene promoter, which repressed the expression of miR-4767 to promote the expression of cGAS.Taken together, our findings demonstrated that HDAC3 played a pivotal role in mediating pyroptosis in macrophage and ALI by activating cGAS/STING pathway through its histone deacetylation function.Targeting HDAC3 in macrophage may provide a new therapeutic target for the prevention of LPS-induced ALI.