Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats
Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats
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DOI：
10.1111/nmo.12127
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发表时间：
2013-06-01
影响因子：
3.5
通讯作者：
Soderholm, J. D.
中科院分区：
文献类型：
--
作者：
Keita, A. V.;Carlsson, A. H.;Soderholm, J. D.
背景血管活性肠肽（VIP）是肠屏障功能和炎症的调节因子。我们的目的是阐明VIP在大鼠应激后卵泡相关上皮（FAE）和绒毛上皮（VE）通透性以及对人肠屏障功能的作用。方法大鼠腹腔注射（i. p.）与VIP受体拮抗剂（抗-VPAC）、肥大细胞稳定剂、doxantrazole（DOX）或NaCl一起，并经受急性避水应激。将回肠段固定在Ussing室中，以评估51铬-EDTA（51 Cr-edta）和大肠杆菌（E.）大肠杆菌（菌株K-12）渗透性。将大鼠回肠和人回肠和结肠段暴露于VIP +/-抗-VPAC或DOX。人FAE的体外共培养模型用于研究上皮-VIP效应。通过显微镜评估VIP/VPAC分布。压力增加了VE和FAE中51 Cr-edta和大肠杆菌的渗透性。通过腹膜内注射DOX或抗VPAC消除了增加。回肠VIP暴露离体增加细菌通过，并且这被DOX减少。在离体人FAE中，VIP处理使细菌摄取加倍，其通过DOX或抗VPAC标准化。在人结肠组织中未观察到屏障效应。在大鼠和人回肠滤泡中发现VPAC，部分肥大细胞共定位。共培养模型证实了VIPmast细胞与上皮细胞在屏障功能调节中的相互作用。结论与推论应激通过VIP和VPAC对粘膜肥大细胞的作用影响FAE屏障。我们认为VIP在控制回肠通透性中的调节作用可能与应激相关肠道疾病中细菌-上皮相互作用有关。
Background Vasoactive intestinal polypeptide (VIP) has been implicated as a regulator of intestinal barrier function and inflammation. Our aim was to elucidate the role of VIP in follicle-associated epithelium (FAE) and villus epithelium (VE) permeability following stress in rats and on human intestinal barrier function. Methods Rats were injected intraperitoneally (i.p.) with VIP receptor-antagonists (anti-VPACs), a mast cell stabilizer, doxantrazole (DOX), or NaCl, and submitted to acute water avoidance stress. Ileal segments were mounted in Ussing chambers to assess 51chromium-edta (51Cr-edta) and Escherichia (E.) coli (strain K-12) permeability. Rat ileal and human ileal and colonic segments were exposed to VIP +/- anti-VPACs or DOX. An in vitro co-culture model of human FAE was used to study epithelial-VIP effects. VIP/VPACs distribution was assessed by microscopy. Key Results Stress increased 51Cr-edta and E.coli permeability in VE and FAE. The increases were abolished by i.p. injection of DOX or anti-VPACs. Ileal VIP-exposure ex vivo increased bacterial passage and this was reduced by DOX. In human FAE ex vivo, VIP treatment doubled bacterial uptake, which was normalized by DOX or anti-VPACs. No barrier effects were observed in human colonic tissue. VPACs were found in rat and human ileal follicles, with partial mast cell co-localization. The co-culture model confirmed VIPmast cellepithelial interactions in the regulation of barrier function. Conclusions & Inferences Stress affects the FAE barrier by mechanisms involving VIP and VPACs on mucosal mast cells. We suggest a regulatory role for VIP in the control of ileal permeability that may be relevant to bacterialepithelial interactions in stress-related intestinal disorders.