Oxygen free radicals in interleukin-1β-induced glycosaminoglycan production by retro-ocular fibroblasts from normal subjects and Graves' ophthalmopathy patients

Rui Lu, Penghai Wang, Leonard Wartofsky, Brian D. Sutton, Jay L. Zweier, Rebecca S. Bahn, James Garrity, Kenneth D. Burman

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Abstract

Graves' ophthalmopathy (GO) is attributed to an autoimmune process that results in the accumulation in retro-ocular 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-1β-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-β 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.

Original languageEnglish (US)
Pages (from-to)297-303
Number of pages7
JournalThyroid
Volume9
Issue number3
DOIs
StatePublished - Mar 1999

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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