Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue.
Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue.
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DOI：
10.1038/s41598-018-31125-x
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发表时间：
2018-08-27
影响因子：
4.6
通讯作者：
Wehkamp J
中科院分区：
文献类型：
--
作者：
Stebe-Frick S;Ostaff MJ;Stange EF;Malek NP;Wehkamp J
组蛋白脱乙酰酶抑制 (HDACi) 被认为是一种有前途的方法，可增强 TLR 介导的抗菌肽（例如人 β-防御素 2 (hBD2)）的诱导。在炎症性肠病 (IBD) 中，与溃疡性结肠炎 (UC) 患者相比，克罗恩病 (CD) 患者的 hBD2 表达减弱。在这里，我们的目的是研究将 HDACi 与治疗性大肠杆菌 Nissle 1917 (EcN)（一种强 hBD2 诱导剂）相结合是否可能是进一步改变保护性免疫反应的可行策略。单层上皮细胞系与健康对照以及 CD 和 UC 患者的培养人体活检样本相比，显示出不同的效果。在单细胞系统中，我们观察到 HDACi 后 TLR 和 IL1β 介导的 hBD2 诱导均出现强烈的 NF-kB 依赖性增强。相反，多细胞结肠活检培养显示相反的结果，并且在所有测试的患者组中，HDACi 与 TLR 介导的 hBD2 诱导的废除相关。值得注意的是，与 UC 患者相比，CD 患者表现出大肠杆菌 Nissle 对 hBD2 的诱导减弱。我们得出的结论是，HDAC 在 hBD2 调节中的作用是上下文相关的，并且可能会受到不同细胞类型的影响。不同 IBD 实体的差异诱导表明基于仍未知的 hBD2 相关机制的不同临床反应模式。
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.
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影响因子：
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