Department of Internal Medicine, University of Michigan, Ann Arbor, 48109, USA.
Prostaglandins Leukot Essent Fatty Acids. 2011 Mar-Apr;84(3-4):113-21. doi: 10.1016/j.plefa.2010.10.003. Epub 2010 Dec 28.
We undertook this study to determine the role of Microsomal PGE Synthase-1 (mPGES-1), and mPGES-1-generated Prostaglandin (PG) E2 on Dendritic Cell (DC) phenotype and function. Using mPGES-1 KnockOut (KO) mice, we generated bone marrow derived DCs and determined their eicosanoid production profile, cell surface marker expression, and cytokine production. We also assessed DC migratory and functional capacity in vivo. Compared to wild-type, mPGES-1 deficient DCs exhibited a markedly attenuated increase in PGE2 production upon LPS stimulation, and displayed preferential shunting towards PGD2 production. mPGES-1 KO DCs did not display deficiencies in maturation, migration or ability to sensitize T cells. However, mPGES-1 deficient DCs generated reduced amounts of the Th1 cytokine IL-12, which may in part be due to increased PGD2 rather than decreased PGE2. These findings provide useful information on the effects of inducible PGE2 on the innate immune system, and have important implications regarding potential consequences of pharmacologic mPGES-1 inhibition.
我们进行这项研究旨在确定微粒体前列腺素 E 合酶-1（mPGES-1）以及 mPGES-1 生成的前列腺素 E2（PG E2）在树突状细胞（DC）表型和功能中的作用。我们使用 mPGES-1 敲除（KO）小鼠生成骨髓来源的 DC，并确定它们的类二十烷酸产物谱、细胞表面标志物表达和细胞因子产生情况。我们还评估了 DC 在体内的迁移和功能能力。与野生型相比，mPGES-1 缺陷型 DC 在 LPS 刺激下产生 PGE2 的增加明显减弱，并且表现出向 PGD2 产生的优先转移。mPGES-1 KO DC 没有表现出成熟、迁移或致敏 T 细胞能力的缺陷。然而，mPGES-1 缺陷型 DC 产生的 Th1 细胞因子 IL-12 量减少，这部分可能是由于 PGD2 增加而不是 PGE2 减少所致。这些发现为诱导型 PGE2 对固有免疫系统的影响提供了有用的信息，并对药理学 mPGES-1 抑制的潜在后果具有重要意义。
