Opioid-induced chemokine expression requires NF-κB activity: the role of PKCζ
Opioid-induced chemokine expression requires NF-κB activity: the role of PKCζ
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DOI：
10.1189/jlb.0710402
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发表时间：
2011-02-01
影响因子：
5.5
通讯作者：
Rogers, Thomas J.
中科院分区：
文献类型：
--
作者：
Happel, Christine;Kutzler, Michele;Rogers, Thomas J.
阿片受体激动剂可诱导广泛的免疫调节活性，从而显着改变宿主防御和炎症反应。先前的研究表明，MOR 选择性激动剂 DAMGO 能够增加人 PBMC 中促炎趋化因子 CCL2、CCL5 和 CXCL10 的表达。 NF-kappa B 是一种转录因子，在先天性和适应性免疫反应中发挥着关键作用。我们报告说，NF-kappa B 在 DAMGO 诱导、MOR 介导的趋化因子表达调节中发挥着重要作用。结果表明，NF-κ B 抑制剂可阻止 DAMGO 给药后诱导 CCL2 表达，并且 NF-κ B 亚基 p65 在丝氨酸残基 311 和 536 处被磷酸化，以响应 MOR 激活。此外，我们证明 PKC zeta 在 DAMGO 诱导的 MOR 激活后被磷酸化，并且该激酶对于 NF-kappa B 激活以及 CCL2 表达和转录活性至关重要。最后，ChIP 分析显示 DAMGO 给药诱导 p65 与 CCL2 启动子的增强子区域结合。这些数据与 MOR 激活促进促炎反应（涉及 NF-κ B 激活）的观点一致。我们的结果还表明 PKC zeta 作为 MOR 介导的促炎趋化因子表达调节的重要参与者具有重要且新颖的作用。 J.洛科克。生物。 89：301-309； 2011年。
Opioid receptor agonists induce broad immunomodulatory activity, which substantially alters host defense and the inflammatory response. Previous studies have shown that the MOR selective agonist DAMGO has the capacity to increase the expression of the proinflammatory chemokines CCL2, CCL5, and CXCL10 in human PBMCs. NF-kappa B is a transcription factor that plays a pivotal role in innate and adaptive immune responses. We report that NF-kappa B is a vital player in the DAMGO-induced, MOR-mediated regulation of chemokine expression. Results show that NF-kappa B inhibitors prevent the induction of CCL2 expression in response to DAMGO administration and that the NF-kappa B subunit, p65, is phosphorylated at serine residues 311 and 536 in response to MOR activation. Furthermore, we demonstrate that PKC zeta is phosphorylated following DAMGO-induced MOR activation, and this kinase is essential for NF-kappa B activation as well as CCL2 expression and transcriptional activity. Finally, ChIP analysis shows that DAMGO administration induces binding of p65 to the enhancer region of the CCL2 promoter. These data are consistent with the notion that MOR activation promotes a proinflammatory response, which involves NF-kappa B activation. Our results also suggest a significant and novel role for PKC zeta as an essential participant in the MOR-mediated regulation of proinflammatory chemokine expression. J. Leukoc. Biol. 89: 301-309; 2011.