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The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880801/ https://www.ncbi.nlm.nih.gov/pubmed/29622848 http://dx.doi.org/10.1267/ahc.17033 |
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author | Ali, Mohmand Noor Choijookhuu, Narantsog Takagi, Hideaki Srisowanna, Naparee Nguyen Nhat Huynh, Mai Yamaguchi, Yuya Synn Oo, Phyu Tin Htwe Kyaw, Myat Sato, Katsuaki Yamaguchi, Ryoji Hishikawa, Yoshitaka |
author_facet | Ali, Mohmand Noor Choijookhuu, Narantsog Takagi, Hideaki Srisowanna, Naparee Nguyen Nhat Huynh, Mai Yamaguchi, Yuya Synn Oo, Phyu Tin Htwe Kyaw, Myat Sato, Katsuaki Yamaguchi, Ryoji Hishikawa, Yoshitaka |
author_sort | Ali, Mohmand Noor |
collection | PubMed |
description | 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)-α, 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-α, 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. |
format | Online Article Text |
id | pubmed-5880801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY |
record_format | MEDLINE/PubMed |
spelling | pubmed-58808012018-04-05 The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis Ali, Mohmand Noor Choijookhuu, Narantsog Takagi, Hideaki Srisowanna, Naparee Nguyen Nhat Huynh, Mai Yamaguchi, Yuya Synn Oo, Phyu Tin Htwe Kyaw, Myat Sato, Katsuaki Yamaguchi, Ryoji Hishikawa, Yoshitaka Acta Histochem Cytochem Regular Article 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)-α, 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-α, 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. JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY 2018-02-27 2018-02-21 /pmc/articles/PMC5880801/ /pubmed/29622848 http://dx.doi.org/10.1267/ahc.17033 Text en 2018 The Japan Society of Histochemistry and Cytochemistry This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Regular Article Ali, Mohmand Noor Choijookhuu, Narantsog Takagi, Hideaki Srisowanna, Naparee Nguyen Nhat Huynh, Mai Yamaguchi, Yuya Synn Oo, Phyu Tin Htwe Kyaw, Myat Sato, Katsuaki Yamaguchi, Ryoji Hishikawa, Yoshitaka The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis |
title | The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis |
title_full | The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis |
title_fullStr | The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis |
title_full_unstemmed | The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis |
title_short | The HDAC Inhibitor, SAHA, Prevents Colonic Inflammation by Suppressing Pro-inflammatory Cytokines and Chemokines in DSS-induced Colitis |
title_sort | hdac inhibitor, saha, prevents colonic inflammation by suppressing pro-inflammatory cytokines and chemokines in dss-induced colitis |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880801/ https://www.ncbi.nlm.nih.gov/pubmed/29622848 http://dx.doi.org/10.1267/ahc.17033 |
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