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SIRT1 alleviates isoniazid-induced hepatocyte injury by reducing histone acetylation in the IL-6 promoter region.

Abstract：

:Silent information regulator 1 (SIRT1) is a type III histone deacetylase that is related to the inhibition of the inflammatory response. The aim of this study was to investigate the regulation of SIRT1 on isoniazid-induced hepatocyte injury and the possible mechanism of histone modification. We found that compared with the blank control group, expression of SIRT1 was decreased in the isoniazid group and that expression of NF-κB p65 was increased, leading to an increase of the expression of inflammatory cytokines Interleukin-6 (IL-6) and Tumour necrosis factor alpha (TNF-α). The level of histone H3K9 acetylation in the promoter region of IL-6 was increased as well. Addition of a SIRT1 agonist (SRT1720) alleviated the inflammatory reaction caused by isoniazid, while the use of a SIRT1 inhibitor (EX527) aggravated the inflammatory damage to cells. In conclusion, these findings indicated that during the period of isoniazid-induced hepatocyte injury, SIRT1 levels were decreased and inflammatory factor levels were increased. Activation of SIRT1 may reduce hepatocyte injury by reducing the level of histone H3K9 acetylation in the promoter region of the IL-6 gene.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Zhang Y,Li Y,Li J,Li B,Chong Y,Zheng G,Sun S,Feng F

doi

10.1016/j.intimp.2018.11.054

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

348-355

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(18)30577-0

journal_volume

67

pub_type

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