Coinduction of Nitric Oxide Synthase and Arginine Metabolic Enzymes in Endotoxin-induced Uveitis Rats

Abstract

The regulation of expression of the arginine-recycling enzymes and arginase isoforms in association with inducible nitric oxide synthase (iNOS) in the eye of endotoxin-induced uveitis (EIU) rats is investigated. An animal model of EIU was created in Wistar rats by intravitreal injection of lipopolysaccharide (LPS). mRNAs for argininosuccinate synthase (AS) and arginase I as well as for iNOS, measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), were induced in the eye of EIU rats. iNOS mRNA increased markedly 3hr after injection, reached a maximum at 6–12hr, and then decreased at 24hr. AS mRNA remained little change at 3hr and increased maximally at 6hr (by about 3.3-fold), whereas arginase I mRNA increased later and reached a maximum at 12hr (by about 4.2-fold). iNOS, AS, and arginase I proteins were also induced. AL and arginase II mRNAs remained little changed. In immunohistochemical analysis, iNOS, AS and arginase I were almost colocalized in infiltrated inflammatory cells in the vitreous, iris, ciliary body and inner layers of the retina. In conclusion, AS and arginase I are coinduced with iNOS in infiltrated inflammatory cells in the eyes of EIU rats, and may regulate NO production by changing intracellular concentration of arginine.