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S. Lee, J.–B. Chae, S.–Y. Kim, J.–G. Kim, Y.–H. Yoon; Increased trnasglutaminase activity in endotoxin–induced uveitis (EIU) . Invest. Ophthalmol. Vis. Sci. 2004;45(13):570.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Transglutaminase (Tgase) 2 is a calcium–dependent enzyme that catalyzes the covalent cross–linking of glutamine and lysine residues in peptides. Several physiological roles for TGase 2 have been demonstrated, such as wound healing, fibrosis, apoptotis, and matrix formation. Increased since TGase2 is induced in many inflammatory diseases, such as celiac disease, Crohn disease, and sporadic inclusion–body myositis, and contributes to inflammatory cascades. Recently, Sohn and colleagues have shown that TGase 2 inhibitors can reverse the inflammation of allergic conjunctivitis (J. Clin. Invest. 2003).This increased activity of TGase in response to inflammatory stimulus may be valuable to further investigations of the effect of TGase inhibitors on various ocular inflammatory disease. Here we have examined whether transglutaminase activity changes also in EIU. Methods:EIU in Lewis rats was induced by footpad injection of 500ug/kg of Salmonella typhimurium endotoxin. At various time points (4– 36 hours) after LPS injection, the eyes were evaluated clinically. Concurrently, aqueous humor was sampled and analyzed for the TGase crosslinking products by western blotting. For histologic studies, the eyeballs were enucleated and stained with hematoxylin and eosin (H&E). Results:Clinically, inflammatory responses such as iris hyperemia and freely moving anterior chamber cells peaked in 24 to 28 hrs. TGase activity was present at low level at the beginning of inflammation, but significantly increased 12 hr to 30 hr after endotoxin treatment. Also the cross–linked proteins (TGase catalytic products) are increased dramatically from 4 hour after LPS injection and show peak at 24–30 hour after LPS injection. Histological findings confirmed the presence of inflammation in the ciliary body and anterior chamber. Conclusions:TGase expression is increased in the response to an inflammatory stimulus in EIU model.
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