Ruzicka B B, Thompson R C, Watson S J, Akil H
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0720, USA.
J Neurochem. 1996 Jan;66(1):425-8. doi: 10.1046/j.1471-4159.1996.66010425.x.
Opioids have been found to modulate the immune system by regulating the function of immunocompetent cells. Several studies suggest that the interaction between immune and opioid systems is not unidirectional, but rather reciprocal, in nature. In the CNS, one cellular target of immune system activation is the astrocytes. These glial cells have been shown to produce the opioid peptide, proenkephalin, to express the mu-, delta-, and kappa-opioid receptors, and to respond to the immune factor interleukin-1 beta (IL1 beta) with an increased proenkephalin synthesis. To characterize more completely the astrocytic opioid response to immune factor stimulation, we examined the effect of IL1 beta (1 ng/ml) on the mu-receptor mRNA expression in primary astrocyte-enriched cultures derived from rat (postnatal day 1-2) cortex, striatum, cerebellum, hippocampus, and hypothalamus. A 24-h treatment with IL1 beta produced a 70-80% increase in the mu-receptor mRNA expression in the striatal, cerebellar, and hippocampal cultures but had no effect on this expression in the cortical and hypothalamic cultures. This observation represents one of the few demonstrated increases in levels of the mu-receptor mRNA in vitro or in vivo, since the cloning of the receptor. The enhanced mu-receptor mRNA expression, together with the previous observation that IL1 beta stimulates proenkephalin synthesis in astrocytes, supports the IL1 beta-mediated regulation of an astroglial opioid peptide and receptor in vitro, a phenomenon that may be significant in the modulation of the gliotic response to neuronal damage. Therefore, the astroglial opioid "system" may be important in the IL1 beta-initiated, coordinated response to CNS infection, trauma, or injury.
已发现阿片类药物可通过调节免疫活性细胞的功能来调节免疫系统。多项研究表明，免疫系统与阿片类药物系统之间的相互作用本质上并非单向的，而是相互的。在中枢神经系统中，免疫系统激活的一个细胞靶点是星形胶质细胞。这些神经胶质细胞已被证明可产生阿片肽脑啡肽原，表达μ-、δ-和κ-阿片受体，并对免疫因子白细胞介素-1β（IL1β）作出反应，使脑啡肽原合成增加。为了更全面地描述星形胶质细胞对免疫因子刺激的阿片类反应，我们研究了IL1β（1纳克/毫升）对源自大鼠（出生后第1 - 2天）皮质、纹状体、小脑、海马体和下丘脑的原代星形胶质细胞富集培养物中μ-受体mRNA表达的影响。用IL1β处理24小时后，纹状体、小脑和海马体培养物中的μ-受体mRNA表达增加了70 - 80%，但对皮质和下丘脑培养物中的这种表达没有影响。自该受体克隆以来，这一观察结果代表了体外或体内μ-受体mRNA水平少数已证实的增加之一。μ-受体mRNA表达的增强，以及之前观察到的IL1β刺激星形胶质细胞中脑啡肽原合成，支持了体外IL1β介导的星形胶质细胞阿片肽和受体的调节，这一现象在调节对神经元损伤的胶质细胞反应中可能具有重要意义。因此，星形胶质细胞阿片类“系统”可能在IL1β引发的对中枢神经系统感染、创伤或损伤的协调反应中起重要作用。
