Expression of Prostaglandin E Synthases in Periodontitis Immunolocalization and Cellular Regulation
Expression of Prostaglandin E Synthases in Periodontitis Immunolocalization and Cellular Regulation
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DOI：
10.1016/j.ajpath.2010.12.048
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发表时间：
2011-04-01
影响因子：
6
通讯作者：
Yucel-Lindberg, Tulay
中科院分区：
文献类型：
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作者：
Bage, Tove;Kats, Anna;Yucel-Lindberg, Tulay
炎症介质前列腺素E-2（PGE（2））与慢性炎症性疾病（包括牙周炎）的发病机制有关;它由环氧合酶（考克斯）和前列腺素E脱氢酶mPGES-1、mPGES-2和cPGES合成。本文研究了PGES在牙周炎患者牙龈组织中的分布，以及这些酶在炎症诱导的不同类型细胞合成PGE（2）中的作用。在牙龈活组织检查中，在成纤维细胞和内皮细胞、平滑肌细胞、上皮细胞和免疫细胞中观察到PGES阳性染色。为了进一步探索PGES对炎症诱导的PGE（2）产生的作用，使用成纤维细胞和内皮细胞、平滑肌细胞和肥大细胞进行体外细胞培养实验。所有细胞类型均表达PGES和考克斯-2，导致PGE（2）合成处于基础水平。然而，在对肿瘤坏死因子（TNF-α）、IL-1 β和共培养的淋巴细胞的反应中，mPGES-1和考克斯-2蛋白在成纤维细胞和平滑肌细胞中的表达增加，并伴随着PGE的增加，而mPGES-2和cPGES不受影响。在内皮细胞中，TNF-α仅通过考克斯-2表达增加PGE（2）的产生，而在肥大细胞中，细胞因子不影响PGE（2）酶的表达或PGE（2）的产生。此外，与野生型成纤维细胞相比，来自mPGES-1敲除小鼠的牙龈成纤维细胞中PGE（2）的产生减少。这些结果表明，成纤维细胞和平滑肌细胞是mPGES-1的重要来源，这可能有助于炎症性牙周炎中PGE（2）的产生增加。(Am病理学杂志2011，178：1676-1684。DOI：10.1016/j.ajpath.2010.12.048）
The inflammatory mediator prostaglandin E-2 (PGE(2)) is implicated in the pathogenesis of chronic inflammatory diseases including periodontitis; it is synthesized by cyclooxygenases (COX) and the prostaglandin E synthases mPGES-1, mPGES-2, and cPGES. The distribution of PGES in gingival tissue of patients with periodontitis and the contribution of these enzymes to inflammation-induced PGE(2) synthesis in different cell types was investigated. In gingival biopsies, positive staining for PGES was observed in fibroblasts and endothelial, smooth muscle, epithelial, and immune cells. To further explore the contribution of PGES to inflammation-induced PGE(2) production, in vitro cell culture experiments were performed using fibroblasts and endothelial, smooth muscle, and mast cells. All cell types expressed PGES and COX-2, resulting in basal levels of PGE(2) synthesis. In response to tumor necrosis factor (TNF-alpha), IL-1 beta, and cocultured lymphocytes, however, mPGES-1 and COX-2 protein expression increased in fibroblasts and smooth muscle cells, accompanied by increased PGE(2), whereas mPGES-2 and cPGES were unaffected. In endothelial cells, TNF-alpha increased PGE(2) production only via COX-2 expression, whereas in mast cells the cytokines did not affect PGE(2) enzyme expression or PGE(2) production. Furthermore, PGE(2) production was diminished in gingival fibroblasts derived from mPGES-1 knockout mice, compared with wild-type fibroblasts. These results suggest that fibroblasts and smooth muscle cells are important sources of mPGES-1, which may contribute to increased PGE(2) production in the inflammatory condition periodontitis. (Am J Pathol 2011, 178:1676-1684. DOI: 10.1016/j.ajpath.2010.12.048)