title: Oxygen free radicals in interleukin-1beta-induced glycosaminoglycan production by retro-ocular fibroblasts from normal subjects and Graves' ophthalmopathy patients.
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)-1beta-induced oxygen free radical production and the role of oxygen free radicals in IL-1beta-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-1beta increased the free radical production in both cells. Superoxide dismutase (SOD) activity in GO retroocular fibroblasts was higher than that in normal cells. IL-1beta dose- and time-dependently stimulated the SOD activity in both cells, with GO retro-ocular fibroblasts showing less responsiveness. IL-1beta 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-1beta-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-1beta.
authors.affiliation: MedLantic Research Institute, Washington Hospital Center, Washington, DC, USA.
authors.forename: R
authors.initials: R
authors.lastname: Lu
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Wartofsky
authors.forename: B D
authors.initials: BD
authors.lastname: Sutton
authors.forename: J L
authors.initials: JL
authors.lastname: Zweier
authors.forename: R S
authors.initials: RS
authors.lastname: Bahn
authors.forename: J
authors.initials: J
authors.lastname: Garrity
authors.forename: K D
authors.initials: KD
authors.lastname: Burman
mesh_terms: D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D003497:Cyclic N-Oxides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006111:Graves Disease / Q000378:metabolism*; D006801:Humans; D019271:Hypoxanthine / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors; D014969:Xanthine Oxidase / Q000494:pharmacology
chemical_list: D003497:Cyclic N-Oxides; D006025:Glycosaminoglycans; D007375:Interleukin-1; D013481:Superoxides; D019271:Hypoxanthine; C055956:5,5-dimethyl-5-hydroperoxy-1-pyrrolidinyloxy; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase