Dignass A U, Podolsky D K
Department of Medicine, Massachusetts General Hospital, Boston.
Gastroenterology. 1993 Nov;105(5):1323-32. doi: 10.1016/0016-5085(93)90136-z.
After various forms of superficial injury, mucosal integrity is re-established by rapid migration of epithelial cells across the wound margins in a process termed restitution. The aim of the present study was to assess the role of several regulatory peptides produced within the intestinal mucosa in epithelial restitution.
The effects of various cytokines and peptide growth factors were studied in an in vitro model of intestinal epithelial restitution. Standard "wounds" were established in confluent monolayers of the intestinal cell line IEC-6, and migration was quantitated in the presence or absence of the physiologically relevant cytokines transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, interferon gamma (IFN-gamma), and platelet-derived growth factor (PDGF).
Four factors (TGF-alpha, EGF, IL-1 beta, and IFN-gamma) enhanced epithelial cell restitution by 2.3-fold to 5.5-fold. In contrast, IL-6, TNF-alpha, PDGF, and an endotoxin lipopolysaccharide had no effect on cell migration. Enhancement of restitution was independent of proliferation. The restitution-promoting cytokines TGF-alpha, EGF, IL-1 beta, and IFN-gamma increase the production of bioactive TGF-beta 1 peptide in wounded IEC-6 cell monolayer. The promotion of IEC-6 restitution by various cytokines could be completely blocked by addition of immunoneutralizing anti-TGF-beta 1.
These findings suggest that various cytokines that are expressed in intestinal mucosa promote epithelial restitution after mucosal injury through increased production of bioactive TGF-beta 1 in epithelial cells.
在各种形式的浅表损伤后，黏膜完整性通过上皮细胞沿伤口边缘快速迁移这一过程得以重建，该过程称为修复。本研究的目的是评估肠道黏膜内产生的几种调节肽在上皮修复中的作用。
在肠道上皮修复的体外模型中研究了各种细胞因子和肽生长因子的作用。在肠道细胞系IEC-6的汇合单层中建立标准“伤口”，并在存在或不存在生理相关细胞因子转化生长因子（TGF）-α、表皮生长因子（EGF）、白细胞介素（IL）-1β、IL-6、肿瘤坏死因子（TNF）-α、干扰素γ（IFN-γ）和血小板衍生生长因子（PDGF）的情况下对迁移进行定量。
四种因子（TGF-α、EGF、IL-1β和IFN-γ）使上皮细胞修复增强了2.3倍至5.5倍。相比之下，IL-6、TNF-α、PDGF和内毒素脂多糖对细胞迁移没有影响。修复的增强与增殖无关。促进修复的细胞因子TGF-α、EGF、IL-1β和IFN-γ增加了受伤的IEC-6细胞单层中生物活性TGF-β1肽的产生。添加免疫中和抗TGF-β1可完全阻断各种细胞因子对IEC-6修复的促进作用。
这些发现表明，肠道黏膜中表达的各种细胞因子通过增加上皮细胞中生物活性TGF-β1的产生来促进黏膜损伤后的上皮修复。
