Cyclooxygenase-2-issued prostaglandin E2 enhances the production of endogenous IL-10, which down-regulates dendritic cell functions
Cyclooxygenase-2-issued prostaglandin E2 enhances the production of endogenous IL-10, which down-regulates dendritic cell functions
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DOI：
10.4049/jimmunol.168.5.2255
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发表时间：
2002-03-01
影响因子：
4.4
通讯作者：
Gualde, N
中科院分区：
文献类型：
--
作者：
Harizi, H;Juzan, M;Gualde, N
PGE(2)是一种众所周知的免疫调节剂，由树突状细胞（dc）等免疫系统中最有效的APC在免疫反应中产生。我们研究了骨髓源性DC （BM-DC）的PGE(2)生物合成能力以及PG对APC的影响。我们观察到，在LPS暴露后，BM-DC产生PGE(2)和其他促炎介质，如白三烯B-4和NO。与lps诱导的COX-2产生的PGE相比，环氧化酶(COX)-1组成性地存在于BM-DC中，对PGE总量的贡献不显著(2)。外源性PGE(2)处理BM-DC诱导产生大量IL-10和少量IL-12p70。此外，选择性抑制COX-2（而非COX-1）后，PGE(2)和IL-10显著下降，同时IL-12产生恢复，DC刺激电位增强。相比之下，我们没有发现白三烯B4或no的明显作用。鉴于PGE2刺激IL-10的潜力，我们研究了PGE2的抑制作用可能是通过IL-10介导的。我们发现外源性IL-10在COX-2选择性抑制剂NS-398存在时抑制IL-12p70的产生，而PGE2的抑制作用被抗IL-10完全逆转。我们认为cox -2介导的PGE(2)上调IL-10，从而下调IL-12的产生和BM-DC的APC功能。
PGE(2) is a well-known immunomodulator produced in the immune response by APCs, such as dendritic cells (DCs), the most potent APC of the immune system. We investigated the PGE(2) biosynthetic capacity of bone marrow-derived DC (BM-DC) and the effects of PG on the APC. We observed that BM-DC produce PGE(2) and other proinflammatory mediators, such as leukotriene B-4 and NO, after LPS exposure. Constitutively present in BM-DC, cyclooxygenase (COX)-1 did not contribute significantly to the total pool of PGE(2) compared with the LPS-induced COX-2-produced PGE(2). Treatment of BM-DC with exogenous PGE(2) induced the production of large amounts of IL-10 and less IL-12p70. In addition, selective inhibition of COX-2, but not COX-1, was followed by significant decrements in PGE(2) and IL-10, a concomitant restoration of IL-12 production, and an enhancement of DC stimulatory potential. In contrast, we found no demonstrable role for leukotriene B4 or NO. In view of the potential of PGE2 to stimulate IL-10, we examined the possibility that the suppressive effect of PGE(2) is mediated via IL-10. We found that exogenous IL-10 inhibits IL-12p70 production in the presence of NS-398, a COX-2 selective inhibitor, while the inhibitory effects of PGE2 were totally reversed by anti-IL-10. We conclude that COX-2-mediated PGE(2) up-regulates IL-10, which down-regulates IL-12 production and the APC function of BM-DC.