Abstract
Graves' ophthalmopathy (GO) is attributed to an autoimmune process that results in the accumulation in retroocular tissue of glycosaminoglycans (GAG) that are in turn responsible for the development of clinical signs and symptoms. Retro-ocular fibroblasts are thought to be the source of GAG production and deposition in GO. In the present study, we investigated interleukin (IL)-1β-induced oxygen free radical production and the role of oxygen free radicals in IL-lβ-induced GAG production in retro-ocular fibroblasts from both normal subjects and patients with GO. Normal retro-ocular fibroblasts demonstrated no measurable oxygen free radicals whereas GO retro-ocular fibroblasts showed detectable signals by electron paramagnetic resonance (EPR) spectroscopy. IL-1β increased the free radical production in both cells. Superoxide dismutase (SOD) activity in GO retroocular fibroblasts was higher than that in normal cells. IL-1β dose- and time-dependently stimulated the SOD activity in both cells, with GO retro-ocular fibroblasts showing less responsiveness. IL-1β dose-dependently increased [3H]glucosamine incorporation into GAG by both cells. An exogenous oxygen free radical-generating system failed to increase GAG. Scavenging oxygen free radicals by the use of SOD (100 U/mL) and catalase (300 U/mL) partially blocked the IL-1β-induced GAG production in both cells. These results suggest that stress related oxygen free radicals are present in the retro-ocular tissue in GO and that oxygen free radicals are involved in GAG accumulation induced by cytokine IL-1β.
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