Role of HDAC6 Inhibition in Sepsis-induced Acute Respiratory Distress Syndrome (Review)

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2021 Mar 22

PMID 33747162

Citations 5

Authors

Qinghua Zhang

Yan Wang

Danhua Qu

Jinyan Yu

Junling Yang

Affiliations

Soon will be listed here.

Abstract

Acute respiratory distress syndrome (ARDS) induced by sepsis contributes remarkably to the high mortality rate observed in intensive care units, largely due to a lack of effective drug therapies. Histone deacetylase 6 (HDAC6) is a class-IIb deacetylase that modulates non-nuclear protein functions via deacetylation and ubiquitination. Importantly, HDAC6 has been shown to exert anti-cancer, anti-neurodegeneration, and immunological effects, and several HDAC6 inhibitors have now entered clinical trials. It has also been recently shown to modulate inflammation, and HDAC6 inhibition has been demonstrated to markedly suppress experimental sepsis. The present review summarizes the role of HDAC6 in sepsis-induced inflammation and endothelial barrier dysfunction in recent years. It is proposed that HDAC6 inhibition predominantly ameliorates sepsis-induced ARDS by directly attenuating inflammation, which modulates the innate and adaptive immunity, transcription of pro-inflammatory genes, and protects endothelial barrier function. HDAC6 inhibition protects against sepsis-induced ARDS, thereby making HDAC6 a promising therapeutic target. However, HDAC inhibition may be associated with adverse effects on the embryo sac and oocyte, necessitating further studies.

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