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

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  • Ali Mohmand Noor
    Department of Anatomy, Histochemistry and Cell Biology, Faculty of Medicine, University of Miyazaki Laboratory of Veterinary Pathology, Department of Veterinary, Faculty of Agriculture, University of Miyazaki
  • Choijookhuu Narantsog
    Department of Anatomy, Histochemistry and Cell Biology, Faculty of Medicine, University of Miyazaki
  • Takagi Hideaki
    Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki
  • Srisowanna Naparee
    Department of Anatomy, Histochemistry and Cell Biology, Faculty of Medicine, University of Miyazaki
  • Nguyen Nhat Huynh Mai
    Department of Anatomy, Histochemistry and Cell Biology, Faculty of Medicine, University of Miyazaki
  • Yamaguchi Yuya
    Department of Anatomy, Histochemistry and Cell Biology, Faculty of Medicine, University of Miyazaki
  • Synn Oo Phyu
    Department of Anatomy, Histochemistry and Cell Biology, Faculty of Medicine, University of Miyazaki
  • Tin Htwe Kyaw Myat
    Department of Anatomy, Histochemistry and Cell Biology, Faculty of Medicine, University of Miyazaki
  • Sato Katsuaki
    Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki
  • Yamaguchi Ryoji
    Laboratory of Veterinary Pathology, Department of Veterinary, Faculty of Agriculture, University of Miyazaki
  • Hishikawa Yoshitaka
    Department of Anatomy, Histochemistry and Cell Biology, Faculty of Medicine, University of Miyazaki

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<p>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.</p>

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