Morphine modulates NFκB activation in macrophages
Morphine modulates NFκB activation in macrophages
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DOI：
10.1006/bbrc.1998.8415
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发表时间：
1998-04-17
影响因子：
3.1
通讯作者：
Barke, RA
中科院分区：
文献类型：
--
作者：
Roy, S;Cain, KJ;Barke, RA
长期使用吗啡会影响免疫系统，使人容易受到机会性感染。巨噬细胞在抵御入侵病原体的第一道防线中发挥着重要作用。了解吗啡影响巨噬细胞功能的机制将对治疗艾滋病毒和艾滋病相关综合征等感染具有重要的治疗意义。活化的巨噬细胞分泌的两种主要细胞因子是白细胞介素-6 （IL-6）和肿瘤坏死因子α (tnf - α)。我们的研究表明，吗啡对脂多糖（LPS）诱导的IL-6和tnf - α的表达有差异调节作用。纳米摩尔浓度的吗啡与LPS协同作用，增加IL-6和tnf - α的分泌。然而，在微摩尔浓度下，吗啡抑制LPS诱导的IL-6和tnf - α的合成。这两种细胞因子基因的表达都依赖于转录因子NF kappa B的激活。有趣的是，吗啡治疗也通过LPS调节NF kappa B的激活，低剂量吗啡（纳摩尔）预处理导致NF kappa B激活增加。相比之下，高剂量吗啡预处理（微摩尔）导致NF κ B活化显著降低。此外，与纳洛酮可逆转的增强作用不同，吗啡对NF κ B的抑制不能被纳洛酮逆转，这表明非经典阿片受体参与其中。(C) 1998学术出版社。
Chronic use of morphine affects the immune system and predisposes an individual to opportunistic infections. Macrophages play an important role in conferring a first line of defense against invading pathogens. Understanding the mechanisms by Which morphine affects the functioning of macrophages would have significant therapeutic benefit in treatment against infections such as HIV and AIDS related syndromes. Two of the major cytokines secreted by activated macrophages are Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). Our studies show that morphine differentially modulates lipopolysaccharide (LPS) induced expression of IL-6 and TNF-alpha. Nanomolar concentrations of morphine synergize with LPS and augment the secretion of both IL-6 and TNF-alpha. However, at micromolar concentrations morphine inhibits LPS induced synthesis of IL-6 and TNF-alpha. Expression of both these cytokine genes is dependent on the activation of a transcription factor, NF kappa B. Interestingly, morphine treatment also modulated the activation of NF kappa B by LPS, Pretreatment with a low dose of morphine (nanomolar) resulted in an increase in NF kappa B activation. In contrast pretreatment with a high dose of morphine (micromolar) led to a significant decrease in NF kappa B activation. Furthermore unlike the augmentation which was naloxone reversible, the inhibition of NF kappa B by morphine was not reversed by naloxone, suggesting the involvement of a nonclassical opioid receptor. (C) 1998 Academic Press.