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Review article: selective histone deacetylase isoforms as potential therapeutic targets in inflammatory bowel diseases
Author(s) -
Felice C.,
Lewis A.,
Armuzzi A.,
Lindsay J. O.,
Silver A.
Publication year - 2015
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.13008
Subject(s) - histone deacetylase , inflammatory bowel disease , vorinostat , inflammation , hdac6 , medicine , cancer research , microrna , histone , colitis , pharmacology , hdac3 , histone deacetylase 2 , immunology , biology , disease , biochemistry , gene
Summary Background A link between histone deacetylases ( HDAC s) and intestinal inflammation has been established. HDAC inhibitors that target gut‐selective inflammatory pathways represent a potential new therapeutic strategy in patients with refractory inflammatory bowel diseases ( IBD ). Aims To review the use of selective HDAC inhibitors to treat gut inflammation and to highlight potential improvements in selectivity/sensitivity by additional targeting of HDAC ‐regulating micro RNA s (mi RNA s). Methods Original articles and reviews have been identified using PubMed search terms: ‘histone deacetylase’, ‘ HDAC inhibitor’, ‘inflammatory bowel disease’, ‘gut inflammation,’ and ‘micro RNA and HDAC ’. Results The use of butyrate in distal colitis provided the first evidence that inhibition of HDAC s decreases intestinal inflammation in IBD . HDAC inhibitors, such as valproic acid, vorinostat and givinostat, reduce inflammation and tissue damage in experimental murine colitis. Potential mechanisms of action for HDAC inhibitors include increased apoptosis, reduction of pro‐inflammatory cytokine release, regulation of transcription factors and modulation of HDAC ‐regulatory mi RNA s. HDAC 2, HDAC 3, HDAC 6, HDAC 9 and HDAC 10 isoforms seem to be specifically involved in chronic intestinal inflammation, justifying the use of selective inhibitors as new therapeutic strategies in IBD . Controlling mi RNA s for these isoforms can be identified. Conclusions The pro‐inflammatory influence of HDAC s in the gut has been confirmed, but mostly in murine studies. Considerably more human data are required to permit development of selective HDAC inhibitors for IBD treatment. Inhibition of key HDAC isoforms in combination with modulation of HDAC ‐regulatory mi RNA s has potential as a novel therapeutic approach.