title: The Effect of (-)-Epigallocatechin-3-Gallate on IL-1β Induced IL-8 Expression in Orbital Fibroblast from Patients with Thyroid-Associated Ophthalmopathy.
abstract: Orbital fibroblasts have been reported to be an important effector cells for the development of thyroid-associated ophthalmopathy (TAO). Orbital fibroblasts secrete various inflammatory cytokines in response to an inflammatory stimulation, leading to TAO-related tissue swelling. It has also been reported that (-)-epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, has antioxidant and anti-inflammatory properties. In the current study, we investigated the issue of whether or how EGCG affects the interleukin (IL)-1β-induced secretion of IL-8 in human orbital fibroblasts from TAO patients. Treatment with EGCG significantly reduced the level of IL-1β-induced secretion of IL-8 and the expression of IL-8 mRNA. IL-1β-induced the degradation of IκBα, and the phosphorylation of p38 and ERK, and the IL-1β-induced expression of IL-8 mRNA was inhibited by specific inhibitors, such as BAY-117085 for NF-kB, SB203580 for p38, and PD98059 for ERK. In addition, treatment with EGCG inhibited the IL-1β-induced degradation of IκBα, and the phosphorylation of p38 and ERK. However, pre-treatment with antioxidants, NVN and NAC, which suppressed ROS generation, did not reduce IL-8 expression in IL-1β-treated orbital fibroblasts, suggesting that the IL-1β-induced IL-8 expression is not mediated by the generation of ROS. These results show that EGCG suppresses the IL-1β-induced expression of IL-8 through inhibition of the NF-κB, p38, and ERK pathways. These findings could contribute to the development of new types of EGCG-containing pharmacological agents for use in the treatment of TAO.
authors: Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors: Ji-Young
authors: JY
authors: Lee
authors: Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors: Ji-Sun
authors: JS
authors: Paik
authors: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors: Mihee
authors: M
authors: Yun
authors: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors: Seong-Beom
authors: SB
authors: Lee
authors: Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors: Suk-Woo
authors: SW
authors: Yang
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D049970:Graves Ophthalmopathy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D016209:Interleukin-8; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D002392:Catechin; C045651:epigallocatechin gallate; D048051:p38 Mitogen-Activated Protein Kinases