title: The anti-inflammatory effect of cyclooxygenase inhibitors in fibroblast-like synoviocytes from the human temporomandibular joint results from the suppression of PGE2 production.
abstract: BACKGROUND
  Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the management of pain and inflammation. However, little remains known about the effects of NSAIDs on synovitis of the human temporomandibular joint (TMJ). The aims of this study were to investigate the potential anti-inflammatory effects of NSAIDs on synovitis of the TMJ and the inflammatory effects of PGE2 on fibroblast-like synoviocytes (FLS) derived from the TMJ.
  
  
  METHODS
  Human synovial tissue was obtained from patients with internal derangement who underwent arthroscopy of the TMJ. FLSs were prepared from the tissues using the outgrowth method. A COX inhibitor (indomethacin or celecoxib) was added to the IL-1β-stimulated cells in culture. The cells were also stimulated with PGE2 or an EP agonist. The PGE2 production and COX-2 and IL-6 expression levels were examined using enzyme-linked immunosorbent assays, real-time PCR, and a microarray analysis.
  
  
  RESULTS
  COX inhibitors decreased not only PGE2 production, but also the expression of COX-2 and IL-6 in FLS stimulated with IL-1β. EP2 and EP4 were both expressed in the FLS, and the treatment with EP2 and EP4 agonists induced IL-6 production in these cells.
  
  
  CONCLUSIONS
  The COX inhibitors indomethacin and celecoxib reduce the expression of inflammatory factors, such as COX-2 and IL-6, in FLS from the TMJ via suppression of PGE2 production. EP2 and EP4 were the main receptors for PGE2 present in the FLS. The approach used in this study may be useful for revealing how drugs such as NSAIDs affect the cellular functions of FLS from the TMJ.
authors: Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors: Mutsumi
authors: M
authors: Kawashima
authors: Naomi
authors: N
authors: Ogura
authors: Miwa
authors: M
authors: Akutsu
authors: Ko
authors: K
authors: Ito
authors: Toshirou
authors: T
authors: Kondoh
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000068579:Celecoxib; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis / Q000037:antagonists & inhibitors*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists / Q000032:analysis; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000819:agonists / Q000032:analysis; D013449:Sulfonamides / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects* / Q000473:pathology; D013585:Synovitis / Q000473:pathology*; D013705:Temporomandibular Joint Disorders / Q000473:pathology*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D053583:Interleukin-1beta; D015850:Interleukin-6; D011720:Pyrazoles; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib; D015232:Dinoprostone; D007213:Indomethacin
keywords: COX inhibitor; fibroblast-like synoviocyte; interleukin-6; prostaglandin E2; temporomandibular joint