Membrane-associated prostaglandin E synthase-1 is upregulated by proinflammatory cytokines in chondrocytes from patients with osteoarthritis.
Membrane-associated prostaglandin E synthase-1 is upregulated by proinflammatory cytokines in chondrocytes from patients with osteoarthritis.
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DOI：
10.1186/ar1195
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发表时间：
2004
影响因子：
4.9
通讯作者：
Kawai S
中科院分区：
文献类型：
--
作者：
Kojima F;Naraba H;Miyamoto S;Beppu M;Aoki H;Kawai S
前列腺素E合成酶（PGES）是最近发现的花生四烯酸级联的末端酶，包括膜相关PGES (mPGES)-1、mPGES-2和细胞质PGES （cPGES）同工酶。PGES在环氧化酶（COX）下游将前列腺素（PG）H2转化为PGE2。我们研究了PGES同工酶在骨关节炎（OA）患者关节软骨细胞中的表达。用各种细胞因子处理软骨细胞，通过逆转录聚合酶链反应和Northern blotting分析PGES同工酶mRNA的表达，Western blotting分析蛋白表达。免疫荧光显微镜检测mPGES-1的亚细胞定位。用酶联免疫吸附法测定花生四烯酸或PGH2向PGE2的转化。最后，采用免疫组化方法检测骨性关节炎关节软骨组织中mPGES-1蛋白的表达。白细胞介素(IL)-1β或肿瘤坏死因子(TNF)-α显著诱导软骨细胞中mPGES-1 mRNA的表达，而其他细胞因子如IL-4、IL-6、IL-8、IL-10和干扰素-γ对其表达无影响。COX-2在相同条件下也被诱导，但表达模式不同。IL-1β和TNF-α不影响cPGES、mPGES-2和COX-1 mRNA的表达。mPGES-1和COX-2的亚细胞定位在核周区域几乎重合。与6-酮- pgf1 α和血栓素B2相比，IL-1β或TNF-α刺激软骨细胞后，PGE2的产生更大。il -1β刺激的软骨细胞裂解液中PGH2向PGE2的转化（PGES活性）显著增加，MK-886抑制了PGH2向PGE2的转化，对mPGES-1活性有抑制作用。骨性关节炎患者关节软骨中的软骨细胞显示mPGES-1免疫染色阳性。这些结果提示mPGES-1可能在OA发病机制中起重要作用。它也可能是OA患者特异性调节PGE2合成的治疗策略的潜在新靶点。
Prostaglandin E synthase (PGES) including isoenzymes of membrane-associated PGES (mPGES)-1, mPGES-2, and cytosolic PGES (cPGES) is the recently identified terminal enzyme of the arachidonic acid cascade. PGES converts prostaglandin (PG)H2 to PGE2 downstream of cyclooxygenase (COX). We investigated the expression of PGES isoenzyme in articular chondrocytes from patients with osteoarthritis (OA). Chondrocytes were treated with various cytokines and the expression of PGES isoenzyme mRNA was analyzed by the reverse transcription–polymerase chain reaction and Northern blotting, whereas Western blotting was performed for protein expression. The subcellular localization of mPGES-1 was determined by immunofluorescent microscopy. Conversion of arachidonic acid or PGH2 to PGE2 was measured by enzyme-linked immunosorbent assay. Finally, the expression of mPGES-1 protein in OA articular cartilage was assessed by immunohistochemistry. Expression of mPGES-1 mRNA in chondrocytes was significantly induced by interleukin (IL)-1β or tumor necrosis factor (TNF)-α, whereas other cytokines, such as IL-4, IL-6, IL-8, IL-10, and interferon-γ, had no effect. COX-2 was also induced under the same conditions, although its pattern of expression was different. Expression of cPGES, mPGES-2, and COX-1 mRNA was not affected by IL-1β or TNF-α. The subcellular localization of mPGES-1 and COX-2 almost overlapped in the perinuclear region. In comparison with 6-keto-PGF1α and thromboxane B2, the production of PGE2 was greater after chondrocytes were stimulated by IL-1β or TNF-α. Conversion of PGH2 to PGE2 (PGES activity) was significantly increased in the lysate from IL-1β-stimulated chondrocytes and it was inhibited by MK-886, which has an inhibitory effect on mPGES-1 activity. Chondrocytes in articular cartilage from patients with OA showed positive immunostaining for mPGES-1. These results suggest that mPGES-1 might be important in the pathogenesis of OA. It might also be a potential new target for therapeutic strategies that specifically modulate PGE2 synthesis in patients with OA.
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影响因子：
7.5
作者：
Chevalier, X
通讯作者：
Chevalier, X
影响因子：
4.8
作者：
Murakami, M;Naraba, H;Kudo, I
通讯作者：
Kudo, I
影响因子：
4.4
作者：
Claveau, D;Sirinyan, M;Mancini, JA
通讯作者：
Mancini, JA
影响因子：
7
作者：
Barakat, AF;Elson, CJ;Westacott, CI
通讯作者：
Westacott, CI
DOI：
10.1073/pnas.96.13.7220
发表时间：
1999-06-22
影响因子：
11.1
作者：
Jakobsson, PJ;Thorén, S;Samuelsson, B
通讯作者：
Samuelsson, B