CYTOKINE MODULATION OF INTESTINAL EPITHELIAL-CELL RESTITUTION - CENTRAL ROLE OF TRANSFORMING GROWTH-FACTOR-BETA
CYTOKINE MODULATION OF INTESTINAL EPITHELIAL-CELL RESTITUTION - CENTRAL ROLE OF TRANSFORMING GROWTH-FACTOR-BETA
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DOI：
10.1016/0016-5085(93)90136-z
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发表时间：
1993-11-01
期刊：
影响因子：
29.4
通讯作者：
PODOLSKY, DK
中科院分区：
文献类型：
--
作者：
DIGNASS, AU;PODOLSKY, DK
背景资料：在各种形式的浅表损伤后，粘膜完整性通过上皮细胞在称为恢复的过程中快速迁移穿过伤口边缘而重建。本研究的目的是评估肠粘膜内产生的几种调节肽在上皮修复中的作用。方法：在肠上皮重建的体外模型中研究各种细胞因子和肽生长因子的作用。在肠细胞系IEC-6的融合单层中建立标准“伤口”，并在存在或不存在生理学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）的情况下定量迁移。结果：TGF-α、EGF、IL-1β和IFN-γ 4种因子可使上皮细胞修复增强2.3 ~ 5.5倍。相反，IL-6、TNF-α、PDGF和内毒素脂多糖对细胞迁移没有影响。恢复的增强与扩散无关。修复促进细胞因子TGF-α、EGF、IL-1β和IFN-γ可促进损伤IEC-6细胞单层产生具有生物活性的TGF-β1肽。各种细胞因子对IEC-6恢复的促进作用可通过加入免疫中和抗TGF-β1完全阻断。结论：这些发现表明，肠粘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的产生来促进粘膜损伤后的上皮修复。
Background: 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. Methods: 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)-α, epidermal growth factor (EGF), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon gamma (IFN-γ), and platelet-derived growth factor (PDGF). Results: Four factors (TGF-α, EGF, IL-1β, and IFN-γ) enhanced epithelial cell restitution by 2.3-fold to 5.5-fold. In contrast, IL-6, TNF-α, PDGF, and an endotoxin lipopolysaccharide had no effect on cell migration. Enhancement of restitution was independent of proliferation. The restitution-promoting cytokines TGF-α, EGF, IL-1β, and IFN-γ increase the production of bioactive TGF-β1 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-β1. Conclusions: These findings suggest that various cytokines that are expressed in intestinal mucosa promote epithelial restitution after mucosal injury through increased production of bioactive TGF-β1 in epithelial cells.