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首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Opposite regulation of prostaglandin E2 synthesis by transforming growth factor-beta1 and interleukin 10 in activated microglial cultures.
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Opposite regulation of prostaglandin E2 synthesis by transforming growth factor-beta1 and interleukin 10 in activated microglial cultures.

机译：在激活的小胶质细胞培养物中通过转化生长因子-beta1和白介素10来对前列腺素E2合成进行相反的调节。

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We have recently shown that prostaglandin E2 (PGE2) synthesis in activated microglia is tightly regulated by several substances (NO, neurotransmitters, pro-inflammatory cytokines), that might originate from intrinsic brain cells or from hematogenous cells infiltrating the brain in the course of inflammatory diseases. In view of the important immunoregulatory and neuroprotective functions recently attributed to PGE2, in the present study we extended our analysis of factors regulating PGE2 synthesis in rat microglial cultures to two anti-inflammatory and immunosuppressive cytokines, transforming growth factor beta1 (TGF-beta1) and interleukin 10 (IL-10), which share with PGE2 the ability to strongly deactivate peripheral macrophages and microglial cells. Moreover, we looked at the effect of the two cytokines on nitric oxide (NO) synthesis, another important microglial effector, whose synthesis is linked to that of PGE2 by complex feed-back mechanisms. We found that while both cytokines inhibited LPS-induced NO release, they had distinct and opposite regulatory activities on PGE2 production. In fact, while TGF-beta1 enhanced LPS-induced PGE2 synthesis, IL-10 showed an inhibitory effect. The two cytokines acted mainly by regulating the LPS-induced expression of the rate limiting enzymes of the two metabolic pathways, cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS). Moreover, TGF-beta1 counteracted the effect of the pro-inflammatory cytokine interferon-gamma, which in the same cultures has been shown to downregulate PGE2 and to upregulate NO synthesis. Although the present in vitro observations cannot be directly extrapolated to the in vivo situation, they may provide a novel clue for understanding the specific role of TGF-beta1 and IL-10 in several neurological diseases such as multiple sclerosis, in which their cerebral level was found to be elevated.
机译：我们最近发现，活化小胶质细胞中前列腺素E2（PGE2）的合成受到几种物质（NO，神经递质，促炎细胞因子）的严格调控，这些物质可能源自内在的脑细胞或在炎症过程中渗透到大脑的血细胞疾病。鉴于最近归因于PGE2的重要免疫调节和神经保护功能，在本研究中，我们将对大鼠小胶质细胞培养物中调节PGE2合成的因子的分析扩展到两种抗炎和免疫抑制细胞因子，即转化生长因子beta1（TGF-beta1）和白细胞介素10（IL-10），与PGE2共同具有使外周巨噬细胞和小胶质细胞强烈失活的能力。此外，我们研究了这两种细胞因子对一氧化氮（NO）合成的影响，NO是另一种重要的小胶质细胞效应子，其合成与PGE2的合成通过复杂的反馈机制相关。我们发现，虽然两种细胞因子均抑制LPS诱导的NO释放，但它们对PGE2的产生具有独特而相反的调节活性。实际上，尽管TGF-beta1增强了LPS诱导的PGE2合成，但IL-10表现出抑制作用。这两种细胞因子的主要作用是通过调节LPS诱导的两种代谢途径的限速酶环氧合酶2（COX-2）和诱导型一氧化氮合酶（iNOS）的表达。此外，TGF-beta1抵消了促炎性细胞因子干扰素-γ的作用，在相同的培养物中，该作用已被证明可以下调PGE2并上调NO的合成。尽管目前的体外观察不能直接推断到体内情况，但它们可能为理解TGF-β1和IL-10在几种神经系统疾病（如多发性硬化症）中的特定作用提供了新的线索，被发现升高。

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