Effect of tumor necrosis factor alpha on rabbit corneal endothelial permeability.
Effect of tumor necrosis factor alpha on rabbit corneal endothelial permeability.
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发表时间：
1996
影响因子：
4.4
通讯作者：
M. Watsky;Z. Guan;D. N. Ragsdale
中科院分区：
文献类型：
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作者：
M. Watsky;Z. Guan;D. N. Ragsdale
肿瘤坏死因子α（TNF α）存在于虹膜和泪腺中，在炎症和角膜损伤后其浓度增加。虽然TNF α已被证明可增加角膜细胞和角膜上皮白细胞介素的产生，但尚未报道TNF α对角膜内皮细胞的明确影响。TNF α已被证明通过f-肌动蛋白解聚破坏血管内皮细胞单层的屏障功能。细胞内环磷酸腺苷（cAMP）浓度的降低可能在这种反应中发挥作用。本研究旨在研究TNF α调节角膜内皮通透性的作用和信号转导机制。此外，这是第一次检查TNF α对非培养细胞单层屏障功能的影响。方法在角膜内皮显微镜下进行兔角膜内皮细胞灌流。处理角膜用于渗透性测量或f-肌动蛋白染色。结果TNF-α灌流角膜的通透性明显高于对照组。f-肌动蛋白染色显示，与对照相比，TNF α灌流破坏了f-肌动蛋白丝。用f-肌动蛋白稳定剂phallacidin灌注的角膜具有比TNF α灌注对显著更低的渗透性。用TNF α加8-溴-cAMP（0.01至3 mM）灌注的角膜的渗透性在所有浓度下均显著低于TNF α灌注对，尽管仅在0.1 mM cAMP浓度下显著较低。结论：TNF α引起角膜内皮通透性增加，这种增加是由f-肌动蛋白丝的破坏介导的; cAMP似乎参与了这种反应。
PURPOSE Tumor necrosis factor alpha (TNF alpha) is present in the iris and the lacrimal gland, and its concentration is increased during inflammation and after corneal wounding. Although TNF alpha has been shown to increase keratocyte and corneal epithelial interleukin production, no definitive effects of TNF alpha on corneal endothelial cells have been reported. TNF alpha has been shown to disrupt barrier function in vascular endothelial monolayers through f-actin depolymerization. A reduction in intracellular cyclic adenosine monophosphate (cAMP) concentration may play a role in this response. This study was designed to examine the role and signal transduction mechanisms of TNF alpha modulation of endothelial permeability in the cornea. In addition, it is the first examination of the effects of TNF alpha on the barrier function of a noncultured cell monolayer. METHODS Rabbit corneal endothelial superfusions were performed under an in vitro specular microscope. Corneas were processed for permeability measurements or f-actin staining. RESULTS TNF alpha superfused corneas had significantly higher permeabilities than controls. f-actin staining revealed that TNF alpha superfusion disrupted f-actin filaments when compared to controls. Corneas superfused with the f-actin stabilizing agent phallacidin had significantly lower permeabilities than TNF alpha superfused pairs. Permeabilities of corneas superfused with TNF alpha plus 8-bromo-cAMP (0.01 to 3 mM) were significantly lower than TNF alpha superfused pairs at all concentrations, although only significantly lower at the 0.1 mM cAMP concentration. CONCLUSIONS TNF alpha causes an increase in corneal endothelial permeability, and this increase is mediated by disruption of f-actin filaments; cAMP appears to be involved in this response.