Harizi Hedi, Norbert Gualde
CNRS UMR 5540, University Bordeaux 2, Bordeaux, France.
Cell Immunol. 2004 Apr;228(2):99-109. doi: 10.1016/j.cellimm.2004.04.003.
Several endogenously produced mediators, including cytokines such as IL-6, IL-10, and TNF-alpha and prostanoids such as prostaglandin E(2) (PGE(2)), regulate dendritic cell (DC) function and contribute to immune homeostasis. In this study, we report that exogenous PGE(2) enhances the production of IL-10 from bone marrow-derived DC (BM-DC). IL-6, but not TNF-alpha, release is enhanced by PGE(2) in the presence of anti-IL-10, suggesting that endogenous IL-10 masks PGE(2)-induced IL-6. Furthermore, both exogenous IL-10 and PGE(2) inhibit LPS-induced IL-6 and TNF-alpha, whereas selective inhibition of cyclooxygenase-2 (COX-2) or addition of anti-IL-10 causes the reverse effects. Exogenous IL-10, but not IL-6, dose-dependently suppresses COX-2 protein expression and PGE(2) production, and TNF-alpha does not reverse this effect. In contrast, anti-IL-10 up-regulates prostanoid production by LPS-stimulated BM-DC. Taken together, our results show that in response to PGE(2), BM-DC produce IL-10, which in turn down-regulates their own production of IL-6-, TNF-alpha-, and COX-2-derived prostanoids, and plays crucial roles in determining the BM-DC pro-inflammatory phenotype.
几种内源性产生的介质，包括细胞因子如白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和肿瘤坏死因子-α（TNF-α）以及类前列腺素如前列腺素E2（PGE2），调节树突状细胞（DC）功能并有助于免疫稳态。在本研究中，我们报告外源性PGE2增强了骨髓来源的DC（BM-DC）产生IL-10的能力。在存在抗IL-10的情况下，PGE2增强了IL-6的释放，但未增强TNF-α的释放，这表明内源性IL-10掩盖了PGE2诱导的IL-6。此外，外源性IL-10和PGE2均抑制脂多糖（LPS）诱导产生的IL-6和TNF-α，而选择性抑制环氧合酶-2（COX-2）或添加抗IL-10则产生相反的效果。外源性IL-10而非IL-6剂量依赖性地抑制COX-2蛋白表达和PGE2产生，且TNF-α不会逆转这种作用。相反，抗IL-10上调LPS刺激的BM-DC的类前列腺素产生。综上所述，我们的结果表明，响应PGE2时，BM-DC产生IL-10，而IL-10反过来下调其自身IL-6、TNF-α和COX-2衍生的类前列腺素的产生，并在决定BM-DC促炎表型中起关键作用。
