Epithelial injury induces keratocyte apoptosis: Hypothesized role for the interleukin-1 system in the modulation of corneal tissue organization and wound healing
Epithelial injury induces keratocyte apoptosis: Hypothesized role for the interleukin-1 system in the modulation of corneal tissue organization and wound healing
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DOI：
10.1006/exer.1996.0038
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发表时间：
1996-04-01
影响因子：
3.4
通讯作者：
Chwang, EL
中科院分区：
文献类型：
--
作者：
Wilson, SE;He, YG;Chwang, EL
本研究的目的是确定程序性细胞死亡（细胞凋亡）的作用，在角膜上皮清创伤口下的角膜细胞的消失，并探讨白细胞介素-1（IL-1）在诱导细胞凋亡的基质成纤维细胞在体外和角膜细胞在体内的潜在作用。角膜细胞和基质成纤维细胞形态学检查在受伤和未受伤的小鼠角膜，使用透射电子显微镜。用TUNEL法检测细胞核DNA 3 ′-羟基末端的断裂。通过角膜缘穿刺点将IL-1 α微量注射到角膜基质中，测定了IL-1对角膜基质细胞的体内作用。用原代培养的人角膜基质和真皮成纤维细胞测定了白细胞介素-1 α（IL-1 α）和白细胞介素-1 β（IL-1 β）的体外作用。上皮刮伤后，在前基质角膜细胞中检测到细胞皱缩、膜结合体形成、染色质浓缩和断裂以及DNA断裂，与细胞凋亡一致。因此，上皮清创后角膜细胞从下层基质中消失是由细胞凋亡介导的。将IL-1 α微量注射到小鼠角膜中央基质中，通过细胞凋亡和可能的负趋化性引起基质中角膜细胞的重新分布。IL-1 α和IL-1 β在体外诱导角膜基质和真皮成纤维细胞凋亡。上皮/内皮-基质IL-1系统可通过诱导角膜细胞凋亡介导角膜组织的组织化和对机械和病原体诱导的损伤的反应。角膜细胞凋亡可能是角膜手术后伤口愈合的起始事件。我们推测该系统的紊乱可能在圆锥角膜和其他角膜疾病的发病机制中起作用。(C)1996年学术出版社
The purpose of this study was to determine the role of programmed cell death (apoptosis) in the disappearance of keratocytes beneath an epithelial debridement wound in the cornea and to investigate a potential role of interleukin-l (IL-1) in induction of apoptosis in stromal fibroblasts in vitro and keratocytes in vivo. Keratocyte and stromal fibroblast cell morphology was examined in wounded and unwounded mouse corneas using transmission electron microscopy. Nuclear DNA fragmentation was detected with the TUNEL assay for 3'-hydroxyl DNA ends. The effect of IL-1 on keratocytes in vivo was determined by microinjection of IL-1 alpha into the central corneal stroma via a limbal entry site, The in vitro effects of interleukin-1 alpha (IL-1 alpha) and interleukin-l beta (IL-1 beta) were determined with primary cultures of human corneal stromal and dermal fibroblasts. Cell shrinkage, blebbing with formation of membrane bound bodies, condensation and fragmentation of the chromatin, and DNA fragmentation, consistent with apoptosis were detected in anterior stromal keratocytes after epithelial scrape wounds. Thus, disappearance of keratocytes from the underlying stroma following epithelial debridement is mediated by apoptosis. Microinjection of IL-1 alpha into the central stroma of the mouse cornea caused a redistribution of keratocytes in the stroma via apoptosis and, possibly, negative chemotaxis. IL-1 alpha and IL-1 beta induced apoptosis in corneal stromal and dermal fibroblasts in vitro. The epithelial/endothelial-stromal IL-1 system may mediate corneal tissue organization and responses to mechanical- and pathogen-induced injury through induction of keratocyte apoptosis. Keratocyte apoptosis is likely an initiating event in wound healing following corneal surgery. We hypothesize that derangement's in this system may have a role in the pathogenesis of keratoconus and other diseases of the cornea. (C) 1996 Academic Press Limited