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Prostaglandin modulates TLR3-induced cytokine expression in human astroglioma cells

机译:前列腺素调节人星形胶质瘤细胞中TLR3诱导的细胞因子表达

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Cyclooxygenase (COX) products and pattern recognition receptors are important modulators of neuroinflammation; however, the role of prostaglandins and toll-like receptor (TLR) signaling and the functional crosstalk between COX modulators remains unclear, especially in astrocytes that closely modulate neuronal functions. Here, we studied the effect of prostaglandins on toll-like receptor 3 (TLR3)-induced cytokine expression in human astroglioma CRT-MG cells. Prostaglandin E_2 (PGE_2) was shown to increase cytosolic cAMP levels in an EP2 receptor dependent manner. Interestingly, the TLR3 agonist polyinosinicpolycytidylic acid (poly(I:C)) mediated phosphorylation of NF-kB and extracellular stress-related Mnase 1/2 (ERK1/2), which significantly decreased following PGE_2 treatment. In addition, PGE_2 increased the phosphorylation and inactivation of glycogen synthesis kinase-3beta (GSK-30), whereas poly(I:C) decreased it. We observed that PGE_2 decreased tumor necrosis factor-alpha (TNF-alpha) production evoked by poly(I:C), whereas PGE_2 potentiated poly(I:C)-triggered interleukin-8 (IL-8) production. These results suggest that prostaglandin modulates the TLR3-mediated cytokine profile in astrocytes via EP2 receptors and regulates the NF-kB, ERK1/2 and GSK-3beta signaling pathways.
机译:环氧合酶(COX)产物和模式识别受体是神经炎症的重要调节剂。然而,前列腺素和toll样受体(TLR)信号传导的作用以及COX调节剂之间的功能性相互作用仍然不清楚,尤其是在紧密调节神经元功能的星形胶质细胞中。在这里,我们研究了前列腺素对人类星形胶质瘤CRT-MG细胞中Toll样受体3(TLR3)诱导的细胞因子表达的影响。已显示前列腺素E_2(PGE_2)以EP2受体依赖性方式增加胞质cAMP水平。有趣的是,TLR3激动剂聚肌苷酸聚胞苷酸(poly(I:C))介导了NF-kB和细胞外应激相关Mnase 1/2(ERK1 / 2)的磷酸化,在PGE_2处理后,磷酸化显着降低。此外,PGE_2增加了糖原合成激酶-3β(GSK-30)的磷酸化和失活,而聚(I:C)降低了它。我们观察到PGE_2降低了由poly(I:C)引起的肿瘤坏死因子-α(TNF-alpha)的产生,而PGE_2增强了由poly(I:C)触发的白介素8(IL-8)的产生。这些结果表明,前列腺素可通过EP2受体调节星形胶质细胞中TLR3介导的细胞因子谱,并调节NF-kB,ERK1 / 2和GSK-3beta信号通路。

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