Fleisher L N, Ferrell J B, McGahan M C
North Carolina State University, College of Veterinary Medicine, Department of Anatomy, Physiological Sciences and Radiology, Raleigh 27606, USA.
Exp Eye Res. 1995 Feb;60(2):165-71. doi: 10.1016/s0014-4835(95)80007-7.
Despite extensive evidence implicating the cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha) in the intraocular inflammatory response, little is known about their effects on signal transduction in anterior uveal tissue. Since these cytokines have been shown to alter the adenylyl cyclase system in nonocular tissues, we tested the hypothesis that IL-1 beta and TNF alpha affect the anterior uvea by altering production of the intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) in ciliary epithelial bilayers. This was accomplished by measuring the levels of cAMP in bilayers ex vivo, following intraocular inflammation induced by intravitreal injection of IL-1 beta, TNF alpha or bacterial endotoxin, and in vitro, following exposure to IL-1 beta, TNF alpha or bacterial endotoxin. Although cAMP production was enhanced in bilayers from IL-1 beta-, TNF alpha- or endotoxin-inflamed eyes, ex vivo, exposure of normal bilayers to IL-1 beta (15 U ml-1), TNF alpha (20 U ml-1), or a low concentration of endotoxin (0.01 microgram ml-1) for 4 hr, in vitro, had no effect on cAMP production. The inability of IL-1 beta, TNF alpha, or the low concentration of endotoxin to increase cAMP production by bilayers, in vitro, suggests that the enhanced cAMP production observed with inflamed bilayers, ex vivo, was not due to a direct action of these inflammatory agonists on the ciliary epithelial bilayer. Although direct exposure to cytokines or endotoxin did not change cAMP production, treatment with IL-1 beta, TNF alpha, or a higher concentration of endotoxin (1 microgram ml-1) did affect signal transduction mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
尽管有大量证据表明细胞因子白细胞介素 -1（IL -1）和肿瘤坏死因子 -α（TNFα）参与眼内炎症反应，但它们对前葡萄膜组织信号转导的影响却知之甚少。由于这些细胞因子已被证明可改变非眼组织中的腺苷酸环化酶系统，我们测试了这样一个假设，即IL -1β和TNFα通过改变睫状体上皮双层中细胞内第二信使3'，5'-环磷酸腺苷（cAMP）的产生来影响前葡萄膜。这是通过在玻璃体内注射IL -1β、TNFα或细菌内毒素诱导眼内炎症后，测量离体双层中的cAMP水平来实现的，并且在体外，在暴露于IL -1β、TNFα或细菌内毒素后进行测量。尽管来自IL -1β、TNFα或内毒素炎症眼的双层中cAMP产生增加，但在体外，将正常双层暴露于IL -1β（15 U/ml）、TNFα（20 U/ml）或低浓度内毒素（0.01 μg/ml）4小时对cAMP产生没有影响。体外IL -1β、TNFα或低浓度内毒素无法增加双层中的cAMP产生，这表明在离体炎症双层中观察到的cAMP产生增加并非由于这些炎症激动剂对睫状体上皮双层的直接作用。尽管直接暴露于细胞因子或内毒素不会改变cAMP产生，但用IL -1β、TNFα或更高浓度内毒素（1 μg/ml）处理确实会影响信号转导机制。（摘要截短至250字）
