Acetylation of histone 3 promotes miR-29a expression and downregulates STAT3 in sepsis

•IL-6 promotes miR-29a expression.•Acetylation of Histone contributes to IL-6-induced expression of miR-29a.•IL-6 promotes glycolysis and the production of Acetylated CoA.•MiR-29a suppresses LPS-induced sepsis shock by targeting STAT3. MiR-29a targets signal transducers and activators of transcription 3 (STAT3) and negatively regulates its expression. Both miR-29a and STAT3 have been implicated in sepsis and upregulated miR-29a was associated with sepsis. However, the regulation of miR-29a in sepsis is not well elucidated. We treated TC-1 cells with interleukin (IL)-6 and the expression of miR-29a and STAT3 was measured. We pre-treated TC-1 cells with histone deacetylase inhibitor Trichostatin A, DNA methylation inhibitor 5-Azacytidine or histone acetyltransferase inhibitor A-485, then treated cells with IL-6 and analyzed the expression of miR-29a and STAT3. We measured the expression of histone deacetylases and histone acetyltransferase, and glycolysis in IL-6-treated TC-1 cells. We administrated miR-29a inhibitor or STAT3 inhibitor to septic mice and the survival rate and expression of anti-apoptotic factors were measured. IL-6 promoted miR-29a expression while suppressed STAT3 expression. Upregulation of miR-29a was associated with sepsis. Histone acetylation promoted miR-29a expression. IL-6 promoted glycolysis in TC-1 cells, which resulted in Acetyl-CoA accumulation. Inhibition of miR-29a promoted survival rate in septic mice while inhibiting STAT3 exacerbated death in mice. The protection of miR-29a inhibition against sepsis was abolished when STAT3 was inhibited. Histone acetylation promoted miR-29a expression, resulting in downregulation of STAT3 and exacerbation of sepsis.