Yucel-Lindberg Tülay, Hallström Therese, Kats Anna, Mustafa Manal, Modéer Thomas
Department of Pediatric Dentistry, Institute of Odontology, Karolinska Institutet, Box 4064, S-141 04, Huddinge, Sweden.
Inflammation. 2004 Apr;28(2):89-95. doi: 10.1023/b:ifla.0000033024.13748.c1.
It is well established that prostaglandin E2 (PGE2) plays an important role in inflammatory diseases including periodontitis. Previously we have reported that the inflammatory mediators interleukin-1beta, (IL-1beta) and tumor necrosis factor alpha (TNFalpha) stimulate PGE2 synthesis by inducing mRNA expression of cyclooxygenase-2 (COX-2) in human gingival fibroblasts. In present study the involvement of microsomal prostaglandin E synthase-1 (mPGES-1) in relation to PGE2 production was investigated. The results showed that IL-1beta as well as TNFalpha induced mPGES-1 mRNA and protein expression accompanied by enhanced PGE2 production in gingival fibroblasts. The anti-inflammatory steroid dexamethasone (DEX) inhibited mPGES-1 mRNA and protein expression as well as PGE2 production induced by IL-1beta or TNFalpha. The COX-2 specific inhibitor, celecoxib, in contrast to the nonspecific COX inhibitor, indomethacin, markedly reduced mPGES-1 expression induced by IL-1beta. The results demonstrate that mPGES-1 regulates PGE2 production in gingival fibroblasts stimulated by inflammatory mediators IL-1beta and TNFa. This novel pathway may be a potential target for treatment strategies of periodontal disease.
前列腺素E2（PGE2）在包括牙周炎在内的炎症性疾病中发挥重要作用，这一点已得到充分证实。此前我们报道过，炎症介质白细胞介素-1β（IL-1β）和肿瘤坏死因子α（TNFα）通过诱导人牙龈成纤维细胞中环氧合酶-2（COX-2）的mRNA表达来刺激PGE2的合成。在本研究中，我们调查了微粒体前列腺素E合酶-1（mPGES-1）与PGE2产生的关系。结果表明，IL-1β以及TNFα诱导了牙龈成纤维细胞中mPGES-1的mRNA和蛋白表达，同时伴随着PGE2产生的增加。抗炎类固醇地塞米松（DEX）抑制了IL-1β或TNFα诱导的mPGES-1的mRNA和蛋白表达以及PGE2的产生。与非特异性COX抑制剂吲哚美辛相比，COX-2特异性抑制剂塞来昔布显著降低了IL-1β诱导的mPGES-1表达。结果表明，mPGES-1在炎症介质IL-1β和TNFα刺激的牙龈成纤维细胞中调节PGE2的产生。这一新途径可能是牙周病治疗策略的潜在靶点。
Zotero 插件