SIRT1 alleviates isoniazid-induced hepatocyte injury by reducing histone acetylation in the IL-6 promoter region.
Antitubercular Agents
/ adverse effects
Carbazoles
/ pharmacology
Cell Line
Gene Expression Regulation
/ drug effects
Hepatocytes
/ drug effects
Heterocyclic Compounds, 4 or More Rings
/ pharmacology
Histones
/ genetics
Humans
Interleukin-6
/ genetics
Isoniazid
/ adverse effects
Promoter Regions, Genetic
RNA, Messenger
/ genetics
Sirtuin 1
/ genetics
Hepatocyte injury
Histone acetylation
Inflammation
Isoniazid
SIRT1
Journal
International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
06
09
2018
revised:
20
11
2018
accepted:
30
11
2018
pubmed:
24
12
2018
medline:
10
5
2019
entrez:
23
12
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30578970
pii: S1567-5769(18)30577-0
doi: 10.1016/j.intimp.2018.11.054
pii:
doi:
Substances chimiques
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
0
Antitubercular Agents
0
Carbazoles
0
Heterocyclic Compounds, 4 or More Rings
0
Histones
0
Interleukin-6
0
RNA, Messenger
0
SRT1720
0
SIRT1 protein, human
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Isoniazid
V83O1VOZ8L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
348-355Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.