The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis

被引：42

作者：

Ali, Mohmand Noor ^{[1
,3
]}

Choijookhuu, Narantsog ^{[1
]}

Takagi, Hideaki ^{[2
]}

Srisowanna, Naparee ^{[1
]}

Mai Nguyen Nhat Huynh ^{[1
]}

Yamaguchi, Yuya ^{[1
]}

Oo, Phyu Synn ^{[1
]}

Kyaw, Myat Tin Htwe ^{[1
]}

Sato, Katsuaki ^{[2
]}

Yamaguchi, Ryoji ^{[3
]}

Hishikawa, Yoshitaka ^{[1
]}

机构：

[1] Univ Miyazaki, Fac Med, Dept Anat Histochem & Cell Biol, 5200 Kihara, Kiyotake, Miyazaki 8891692, Japan

[2] Univ Miyazaki, Fac Med, Dept Infect Dis, Div Immunol, Kiyotake, Miyazaki, Japan

[3] Univ Miyazaki, Fac Agr, Dept Vet, Lab Vet Pathol, Kiyotake, Miyazaki, Japan

来源：

ACTA HISTOCHEMICA ET CYTOCHEMICA | 2018年 / 51卷 / 01期

基金：

日本学术振兴会;

关键词：

inflammatory bowel disease; histone deacetylase inhibitor; dextran sodium sulfate; pro-inflammatory cytokines and chemokines; HISTONE DEACETYLASE INHIBITORS; BOWEL-DISEASE; INTESTINAL INFLAMMATION; ULCERATIVE-COLITIS; CELLS; MICE; ACETYLATION; MACROPHAGES; ACTIVATION; EXPRESSION;

D O I：

10.1267/ahc.17033

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract that is caused by multiple factors, including dysfunction of the immune system and genetic and epigenetic alterations. Aberrant epigenetic regulation, especially histone acetylation, was found in biopsies from IBD patients and mouse models of colitis, suggesting that an epigenetic treatment approach may be useful for IBD therapy. Therefore, we investigated the effects of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), in a mouse model of dextran sulfate sodium (DSS)-induced colitis. C57BL/6 mice were treated with 1.5% DSS for 5 days and/or SAHA (25 mg/kg BW/day) for 26 days. Levels of mRNA for the pro-inflammatory cytokines, interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, and the chemokines, Ccl2, were examined by qRT-PCR. CD11b, a marker of dendritic cells, macrophages, and monocytes, as well as Ccl2 expression, were examined by immunohistochemistry. IL-6, TNF-alpha, and Ccl2 gene expression peaked on day 5 in DSS-treated mouse colon, whereas SAHA treatment significantly decreased pro-inflammatory gene expression. Ccl2 protein expression resembled Ccl2 gene expression results. Moreover, localization of CD11b showed that migratory inflammatory cells were dramatically decreased by SAHA treatment compared to DSS-treated mouse colon. Thus, we conclude that the HDAC inhibitor, SAHA, attenuates inflammatory changes in DSS-induced colitis by suppressing local secretion of pro-inflammatory cytokines and chemokines and also by suppressing mobilization and accumulation of inflammatory cells.

引用

页码：33 / 40

页数：8

共 30 条

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