title: Celastrol inhibits IL-1β-induced inflammation in orbital fibroblasts through the suppression of NF-κB activity.
abstract: Graves' disease is an autoimmune disease of the thyroid gland, which is characterized by hyperthyroidism, diffuse goiter and Graves' ophthalmopathy (GO). Although several therapeutic strategies for the treatment of GO have been developed, the effectiveness and the safety profile of these therapies remain to be fully elucidated. Therefore, examination of novel GO therapies remains an urgent requirement. Celastrol, a triterpenoid isolated from traditional Chinese medicine, is a promising drug for the treatment of various inflammatory and autoimmune diseases. CCK‑8 and apoptosis assays were performed to investigate cytotoxicity of celastrol and effect on apoptosis on orbital fibroblasts. Reverse transcription‑polymerase chain reaction, western blotting and ELISAs were performed to examine the effect of celastrol on interleukin (IL)‑1β‑induced inflammation in orbital fibroblasts from patients with GO. The results demonstrated that celastrol significantly attenuated the expression of IL‑6, IL‑8, cyclooxygenase (COX)‑2 and intercellular adhesion molecule‑1 (ICAM‑1), and inhibited IL‑1β‑induced increases in the expression of IL‑6, IL‑8, ICAM‑1 and COX‑2. The levels of prostaglandin E2 in orbital fibroblasts induced by IL‑1β were also suppressed by celastrol. Further investigation revealed that celastrol suppressed the IL‑1β‑induced inflammatory responses in orbital fibroblasts through inhibiting the activation of nuclear factor (NF)‑κB. Taken together, these results suggested that celastrol attenuated the IL‑1β‑induced pro‑inflammatory pathway in orbital fibroblasts from patients with GO, which was associated with the suppression of NF-κB activation.
authors.affiliation: Department of Endocrinology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai 200031, P.R. China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Endocrinology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Longua Medical School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Endocrinology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors.forename: Rongjuan
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Ge
authors.affiliation: Department of Endocrinology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression; D006111:Graves Disease / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D018799:Intercellular Adhesion Molecule-1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C050414:celastrol