Department of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, American university of Beirut, Beirut, Lebanon.
Inflammation group-Nature Conservation Center (NCC) for Sustainable Futures, American University of Beirut, Lebanon.
Sci Rep. 2016 Jul 15;6:29783. doi: 10.1038/srep29783.
Inflammatory bowel disease (IBD) involves functional impairment of intestinal epithelial cells (IECs), concomitant with the infiltration of the lamina propria by inflammatory cells. We explored the reciprocal paracrine and direct interaction between human IECs and macrophages (MΦ) in a co-culture system that mimics some aspects of IBD. We investigated the expression of intercellular junctional proteins in cultured IECs under inflammatory conditions and in tissues from IBD patients. IECs establish functional gap junctions with IECs and MΦ, respectively. Connexin (Cx26) and Cx43 expression in cultured IECs is augmented under inflammatory conditions; while, Cx43-associated junctional complexes partners, E-cadherin, ZO-1, and β-catenin expression is decreased. The expression of Cx26 and Cx43 in IBD tissues is redistributed to the basal membrane of IEC, which is associated with decrease in junctional complex proteins' expression, collagen type IV expression and infiltration of MΦ. These data support the notion that the combination of paracrine and hetero-cellular communication between IECs and MΦs may regulate epithelial cell function through the establishment of junctional complexes between inflammatory cells and IECs, which ultimately contribute to the dys-regulation of intestinal epithelial barrier.
炎症性肠病（IBD）涉及肠上皮细胞（IECs）的功能障碍，同时伴有固有层炎症细胞的浸润。我们在共培养系统中探索了人类 IECs 和巨噬细胞（MΦ）之间的旁分泌和直接相互作用，该系统模拟了 IBD 的某些方面。我们研究了在炎症条件下培养的 IECs 中细胞间连接蛋白的表达以及 IBD 患者组织中的表达。IECs 分别与 IECs 和 MΦ 建立功能性缝隙连接。在炎症条件下，培养的 IECs 中连接蛋白（Cx26）和 Cx43 的表达增加；而 Cx43 相关连接复合体蛋白，E-钙粘蛋白、ZO-1 和 β-连环蛋白的表达减少。Cx26 和 Cx43 在 IBD 组织中的表达重新分布到 IEC 的基膜，这与连接复合体蛋白表达、IV 型胶原表达和 MΦ浸润的减少有关。这些数据支持这样一种观点，即 IECs 和 MΦ 之间的旁分泌和异细胞通讯的结合可能通过在炎症细胞和 IECs 之间建立连接复合体来调节上皮细胞功能，这最终导致肠道上皮屏障的失调。
