The anti-inflammatory effect of cyclooxygenase inhibitors in fibroblast-like synoviocytes from the human temporomandibular joint results from the suppression of PGE2 production.

The anti-inflammatory effect of cyclooxygenase inhibitors in fibroblast-like synoviocytes from the human temporomandibular joint results from the suppression of PGE2 production.
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DOI:
10.1111/jop.12045
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发表时间:
2013-07
期刊:
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
影响因子:
--
通讯作者:
Kondoh T
Kondoh T
中科院分区:
其他
文献类型:
--
作者:
Kawashima M;Ogura N;Akutsu M;Ito K;Kondoh T

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背景 非甾体抗炎药(NSAID)已广泛用于治疗疼痛和炎症。然而,人们对 NSAIDs 对人类颞下颌关节 (TMJ) 滑膜炎的影响知之甚少。本研究的目的是探讨 NSAIDs 对 TMJ 滑膜炎的潜在抗炎作用以及 PGE2 对来自 TMJ 的成纤维样滑膜细胞 (FLS) 的炎症作用。方法从接受颞下颌关节镜检查的内部紊乱患者身上获取人体滑膜组织。使用生长方法从组织中制备 FLS。将 COX 抑制剂(吲哚美辛或塞来考昔)添加到培养中的 IL-1β 刺激细胞中。还用 PGE2 或 EP 激动剂刺激细胞。使用酶联免疫吸附测定、实时 PCR 和微阵列分析检查 PGE2 的产生以及 COX-2 和 IL-6 的表达水平。结果 COX抑制剂不仅降低了IL-1β刺激的FLS中PGE2的产生,而且还降低了COX-2和IL-6的表达。 EP2和EP4均在FLS中表达,并且EP2和EP4激动剂的处理诱导这些细胞中IL-6的产生。结论 COX 抑制剂吲哚美辛和塞来昔布通过抑制 PGE2 的产生,减少 TMJ FLS 中炎症因子(如 COX-2 和 IL-6)的表达。 EP2 和 EP4 是 FLS 中 PGE2 的主要受体。本研究中使用的方法可能有助于揭示 NSAID 等药物如何影响 TMJ 的 FLS 细胞功能。
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. Conclusion 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.
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