Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue

Abstract Histone deacetylase inhibition (HDACi) has been suggested as a promising approach to bolster TLR-mediated induction of antimicrobial peptides such as human β-defensin 2 (hBD2). In inflammatory bowel disease (IBD), Crohn’s disease (CD) patients display an attenuated expression of hBD2 as com...

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Autores principales:	Sabrina Stebe-Frick, Maureen J. Ostaff, Eduard F. Stange, Nisar P. Malek, Jan Wehkamp
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b023f1ee744499bbf6487c14fbb9ce2
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spelling	oai:doaj.org-article:2b023f1ee744499bbf6487c14fbb9ce22021-12-02T15:08:24ZHistone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue10.1038/s41598-018-31125-x2045-2322https://doaj.org/article/2b023f1ee744499bbf6487c14fbb9ce22018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31125-xhttps://doaj.org/toc/2045-2322Abstract Histone deacetylase inhibition (HDACi) has been suggested as a promising approach to bolster TLR-mediated induction of antimicrobial peptides such as human β-defensin 2 (hBD2). In inflammatory bowel disease (IBD), Crohn’s disease (CD) patients display an attenuated expression of hBD2 as compared to ulcerative colitis (UC). Here, we aimed to study if combining HDACi with the therapeutic E. coli Nissle 1917 (EcN), a strong hBD2 inducer, might be a feasible strategy to further modify protective immune responses. Monolayer epithelial cell lines versus cultured human biopsies from healthy controls and CD and UC patients showed diverse effects. In mono-cell systems, we observed a strong NF-kB-dependent enhancement of TLR- but also IL1β-mediated hBD2 induction after HDACi. In contrast, multicellular colonic biopsy culture showed the opposite result and HDACi was associated with an abolished TLR-mediated hBD2 induction in all tested patient groups. Of note, CD patients showed an attenuated induction of hBD2 by E. coli Nissle as compared to UC. We conclude that the role of HDACs in hBD2 regulation is context-dependent and likely modified by different cell types. Differential induction in different IBD entities suggests different clinical response patterns based on still unknown hBD2-associated mechanisms.Sabrina Stebe-FrickMaureen J. OstaffEduard F. StangeNisar P. MalekJan WehkampNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sabrina Stebe-Frick Maureen J. Ostaff Eduard F. Stange Nisar P. Malek Jan Wehkamp Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue
description	Abstract Histone deacetylase inhibition (HDACi) has been suggested as a promising approach to bolster TLR-mediated induction of antimicrobial peptides such as human β-defensin 2 (hBD2). In inflammatory bowel disease (IBD), Crohn’s disease (CD) patients display an attenuated expression of hBD2 as compared to ulcerative colitis (UC). Here, we aimed to study if combining HDACi with the therapeutic E. coli Nissle 1917 (EcN), a strong hBD2 inducer, might be a feasible strategy to further modify protective immune responses. Monolayer epithelial cell lines versus cultured human biopsies from healthy controls and CD and UC patients showed diverse effects. In mono-cell systems, we observed a strong NF-kB-dependent enhancement of TLR- but also IL1β-mediated hBD2 induction after HDACi. In contrast, multicellular colonic biopsy culture showed the opposite result and HDACi was associated with an abolished TLR-mediated hBD2 induction in all tested patient groups. Of note, CD patients showed an attenuated induction of hBD2 by E. coli Nissle as compared to UC. We conclude that the role of HDACs in hBD2 regulation is context-dependent and likely modified by different cell types. Differential induction in different IBD entities suggests different clinical response patterns based on still unknown hBD2-associated mechanisms.
format	article
author	Sabrina Stebe-Frick Maureen J. Ostaff Eduard F. Stange Nisar P. Malek Jan Wehkamp
author_facet	Sabrina Stebe-Frick Maureen J. Ostaff Eduard F. Stange Nisar P. Malek Jan Wehkamp
author_sort	Sabrina Stebe-Frick
title	Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue
title_short	Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue
title_full	Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue
title_fullStr	Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue
title_full_unstemmed	Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue
title_sort	histone deacetylase-mediated regulation of the antimicrobial peptide hbd2 differs in intestinal cell lines and cultured tissue
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/2b023f1ee744499bbf6487c14fbb9ce2
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Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue

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