期刊
EXPERIMENTAL BIOLOGY AND MEDICINE
卷 248, 期 11, 页码 922-935出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/15353702231165707
关键词
Sepsis; acetylation; Akt; SIRT1; macrophages; inflammation
This study reveals that the histone deacetylase SIRT1 can deacetylate Akt protein at Lys14 and Lys20 residues, leading to the suppression of macrophage inflammatory response and thus influencing the progression of sepsis.
Sepsis is characterized by uncontrolled inflammatory response and altered polarization of macrophages at the early phase. Akt is known to drive macrophage inflammatory response. However, how macrophage inflammatory response is fine-tuned by Akt is poorly understood. Here, we found that Lys14 and Lys20 of Akt is deacetylated by the histone deacetylase SIRT1 during macrophage activation to suppress macrophages inflammatory response. Mechanistically, SIRT1 promotes Akt deacetylation to inhibit the activation of NF-kappa B and pro-inflammatory cytokines. Loss of SIRT1 facilitates Akt acetylation and thus promotes inflammatory cytokines in mouse macrophages, potentially worsen the progression of sepsis in mice. By contrast, the upregulation of SIRT1 in macrophages further contributes to the inhibition of pro-inflammatory cytokines via Akt activation in sepsis. Taken together, our findings establish Akt deacetylation as an essential negative regulatory mechanism that curtails M1 polarization.
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