Inflammation induced changes in adenosine 3',5'-cyclic monophosphate production by ciliary epithelial cell bilayers.
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)
Fleisher
L N
LN
North Carolina State University, College of Veterinary Medicine, Department of Anatomy, Physiological Sciences and Radiology, Raleigh 27606, USA.
Ferrell
J B
JB
McGahan
M C
MC
D000818:Animals; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000096:biosynthesis*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014606:Uveitis, Anterior / Q000209:etiology / Q000378:metabolism*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D000242:Cyclic AMP; D007545:Isoproterenol