Inhibition of interleukin-1beta-induced matrix metalloproteinases 1 and 13 production in human osteoarthritic chondrocytes by prostaglandin D2.
Inhibition of interleukin-1beta-induced matrix metalloproteinases 1 and 13 production in human osteoarthritic chondrocytes by prostaglandin D2.
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DOI：
10.1002/art.23958
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发表时间：
2008-11
影响因子：
--
通讯作者：
Fahmi, Hassan
中科院分区：
文献类型：
--
作者：
Zayed, Nadia;Afif, Hassan;Chabane, Nadir;Mfuna-Endam, Leandra;Benderdour, Mohamed;Martel-Pelletier, Johanne;Pelletier, Jean-Pierre;Motiani, Rajender K.;Trebak, Mohamed;Duval, Nicolas;Fahmi, Hassan
探讨前列腺素（PG） D2对白细胞介素-1β (IL-1)诱导的基质金属蛋白酶(MMP)-1和MMP-13在人软骨细胞中表达的影响及PGD2影响的信号通路。用IL-1±PGD2和MMP-1刺激软骨细胞，ELISA法检测MMP-13蛋白表达。通过实时RT-PCR和瞬时转染分别分析mRNA表达和启动子活性。通过特异性激动剂和抗体阻断实验，评估PGD2受体、D前列腺素受体1 （DP1）和Th2细胞上表达的趋化受体样分子（CRTH2）的作用。使用cAMP升高剂和PKA抑制剂来确定cAMP/PKA通路的作用。PGD2剂量依赖性地降低il -1诱导的MMP-1和MMP-13蛋白和mRNA表达及其启动子激活。DP1和CRTH2在软骨细胞中表达和发挥功能。PGD2的作用可被选择性DP1激动剂BW245C模拟，但不能被CRTH2选择性激动剂DK-PGD2模拟。此外，抗DP1抗体可以逆转PGD2的作用，表明PGD2的抑制作用是由DP1介导的。cAMP升高剂8-Br-cAMP和forskolin抑制il -1诱导的MMP-1和MMP-13的表达，PKA抑制剂KT5720和H-89逆转PGD2的抑制作用，提示PGD2的作用是通过cAMP/PKA途径介导的。PGD2通过DP1/cAMP/PKA信号通路抑制il -1诱导的软骨细胞生成MMP-1和MMP-13。这些数据还表明，调节关节中的PGD2水平可能在预防软骨退化方面具有治疗潜力。
To investigate the effects of prostaglandin (PG) D2 on interleukin-1β (IL-1)-induced matrix metalloproteinase (MMP)-1 and MMP-13 expression in human chondrocytes and the signalling pathways involved in the effects of PGD2. Chondrocytes were stimulated with IL-1 ± PGD2 and MMP-1 and MMP-13 protein expression was evaluated by ELISA. mRNA expression and promoter activity were analyzed by real-time RT-PCR and transient transfections, respectively. The role of the PGD2 receptors, D prostanoid receptor 1 (DP1) and chemoattractant-receptor-like molecule expressed on Th2 cells (CRTH2), was evaluated using specific agonists and antibody blocking experiments. The contribution of the cAMP/PKA pathway was determined using cAMP elevating agents and PKA inhibitors. PGD2 dose-dependently decreased IL-1-induced MMP-1 and MMP-13 protein and mRNA expression as well as their promoter activation. DP1 and CRTH2 are expressed and functional in chondrocytes. The effect of PGD2 was mimicked by the selective DP1 agonist BW245C, but not by the CRTH2 selective agonist DK-PGD2. Furthermore, treatment with an anti-DP1 antibody reversed the effect of PGD2, indicating that the inhibitory effect of PGD2 is mediated by DP1. The cAMP elevating agents, 8-Br-cAMP and forskolin, suppressed IL-1-induced MMP-1 and MMP-13 expression, and the PKA inhibitors, KT5720 and H-89, reversed the inhibitory effect of PGD2, suggesting that the effect of PGD2 is mediated by the cAMP/PKA pathway. PGD2 inhibits IL-1-induced MMP-1 and MMP-13 production by chondrocytes through the DP1/cAMP/PKA signalling pathway. These data also suggest that modulation of PGD2 levels in the joint may have therapeutic potential in the prevention of cartilage degradation.
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影响因子：
4.8
作者：
Borden, P;Solymar, D;Heller, RA
通讯作者：
Heller, RA
影响因子：
5.5
作者：
Jakob, M;Démarteau, O;Martin, I
通讯作者：
Martin, I
影响因子：
82.9
作者：
Gilroy, DW;Colville-Nash, PR;Willoughby, DA
通讯作者：
Willoughby, DA
DOI：
10.1084/jem.193.2.255
发表时间：
2001-01-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hirai H;Tanaka K;Yoshie O;Ogawa K;Kenmotsu K;Takamori Y;Ichimasa M;Sugamura K;Nakamura M;Takano S;Nagata K
通讯作者：
Nagata K
影响因子：
--
作者：
dePaulis, A;Marino, I;Marone, G
通讯作者：
Marone, G