Proinflammatory cytokines induce crosstalk between colonic epithelial cells and subepithelial myofibroblasts: Implication in intestinal fibrosis
Proinflammatory cytokines induce crosstalk between colonic epithelial cells and subepithelial myofibroblasts: Implication in intestinal fibrosis
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DOI：
10.1016/j.crohns.2012.04.008
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发表时间：
2013-05-01
影响因子：
8
通讯作者：
Kouroumalis, Elias
中科院分区：
文献类型：
--
作者：
Drygiannakis, Ioannis;Valatas, Vassilis;Kouroumalis, Elias
背景和目的：结肠上皮细胞和邻近的上皮下肌成纤维细胞是肠道炎症和纤维化发病机制中的重要对应物。我们研究了它们之间可能的串扰，同时关注可能引发肠道纤维化的粘膜炎症途径。方法：我们研究了促炎细胞因子（IL-1α、TNF-α、IFN-γ）对人结肠上皮细胞系的影响，以及上皮细胞条件培养基对从正常对照或炎症性克罗恩病患者分离的原代人结肠上皮下肌成纤维细胞以及相应的18CO细胞系的影响。读数包括 TGF-β 和 TIMP-1 的产生、总胶原蛋白合成、基质金属蛋白酶 MMP-2 和 MMP-9 以及肌成纤维细胞迁移/移动性。结果：促炎细胞因子上调结肠上皮细胞中的 TGF-β 和 TIMP-1。来自这些上皮细胞培养物的条件培养基诱导 MMP-9 和胶原蛋白的产生，并抑制上皮下肌成纤维细胞的迁移/活动。 MMP-9 的产生取决于肌成纤维细胞上内皮素受体 A 信号传导。胶原蛋白上调与 TGF-β、CTGF、TF 和内皮素无关。从克罗恩病患者中分离出的上皮下肌成纤维细胞与从正常对照中分离出的上皮下肌成纤维细胞具有相似的反应，但基础胶原蛋白产量较高。结论：我们的研究表明，结肠上皮细胞可能通过诱导与肠纤维化期间观察到的类似的肌成纤维细胞功能来对炎症环境做出反应。 (c) 2012 年欧洲克罗恩病和结肠炎组织。由 Elsevier B.V. 出版。保留所有权利。
Background and aims: Colonic epithelial cells and adjacent subepithelial myofibroblasts are important counterparts in the pathogenesis of intestinal inflammation and fibrosis. We investigated the possible crosstalk between them, whilst focusing on the mucosal inflammation pathways that potentially trigger intestinal fibrosis.Methods: We studied the effects of proinflammatory cytokines (IL-1 alpha, TNF-alpha, IFN-gamma) on human colonic epithelial cell lines and the effects of epithelial cell-conditioned media on primary human colonic subepithelial myofibroblasts isolated from normal controls or patients with inflammatory Crohn's disease along with the corresponding 18CO cell line. Readouts included production of TGF-beta and TIMP-1, total collagen synthesis, matrix metalloproteinases MMP-2 and MMP-9 and myofibroblast migration/mobility.Results: Proinflammatory cytokines upregulated TGF-beta and TIMP-1 in colonic epithelial cells. Conditioned medium from these epithelial cell cultures induced production of MMP-9 and collagen and inhibited the migration/mobility of subepithelial myofibroblasts. MMP-9 production depended on endothelin receptor A signalling on responding myofibroblasts. Collagen upregulation was independent of TGF-beta, CTGF, TF and endothelin. Subepithelial myofibroblasts isolated from Crohn's disease patients had similar responses to those isolated from normal controls, with the exception of higher basal collagen production.Conclusions: Our study indicates that colonic epithelial cells may respond to an inflammatory milieu by inducing myofibroblast functions similar to those observed during intestinal fibrosis. (c) 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.