Fahmi H, Pelletier J-P, Mineau F, Martel-Pelletier J
Osteoarthritis Research Unit, Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Quebec, Canada.
Osteoarthritis Cartilage. 2002 Nov;10(11):845-8. doi: 10.1053/joca.2002.0835.
The PGD(2) metabolite 15-deoxy-delta12,14 PGJ(2) (15d-PGJ(2)), a potent peroxisome proliferator-activated receptor gamma (PPARgamma) activator, has recently received attention for its potential antiinflammatory effects, but its effect on the cyclooxygenase-2 (COX-2) production is still under debate. We investigated the effect of 15d-PGJ(2) on COX-2 and prostaglandin E(2) (PGE(2)) production in the absence or the presence of interleukin-1beta (IL-1beta) in human osteoarthritic chondrocytes.Data showed that, as expected, IL-1beta induced both COX-2 and PGE(2) production. The addition of 15d-PGJ(2) completely blocked (by 93%) the IL-1beta-induced PGE(2) synthesis, whereas COX-2 level was only partially reduced (by 72%). Interestingly in the absence of any COX-2 inducer, 15d-PGJ(2) up-regulated COX-2 expression without concomitant elevation of PGE(2) synthesis. This study showed that the PPARgamma agonist, 15d-PGJ(2), exerts a dual effect on COX-2 production. The mechanisms by which 15d-PGJ(2) favors COX-2 production will be discussed.
前列腺素D2（PGD2）代谢产物15-脱氧-Δ12,14-前列腺素J2（15d-PGJ2）是一种强效的过氧化物酶体增殖物激活受体γ（PPARγ）激活剂，其潜在的抗炎作用最近受到关注，但其对环氧合酶-2（COX-2）产生的影响仍存在争议。我们研究了15d-PGJ2在人骨关节炎软骨细胞中，在不存在或存在白细胞介素-1β（IL-1β）的情况下，对COX-2和前列腺素E2（PGE2）产生的影响。数据显示，正如预期的那样，IL-1β诱导了COX-2和PGE2的产生。添加15d-PGJ2完全阻断了（93%）IL-1β诱导的PGE2合成，而COX-2水平仅部分降低（72%）。有趣的是，在没有任何COX-2诱导剂的情况下，15d-PGJ2上调了COX-2表达，而PGE2合成没有随之升高。这项研究表明，PPARγ激动剂15d-PGJ2对COX-2产生具有双重作用。将讨论15d-PGJ2促进COX-2产生的机制。
