Cell Biology and Immunology Group, Wageningen University, De Elst 1, P.O. Box 338, 6700 AH Wageningen, The Netherlands.
Gen Comp Endocrinol. 2013 Jul 1;188:94-101. doi: 10.1016/j.ygcen.2012.11.010. Epub 2012 Nov 29.
Neuroendocrine- and immune systems interact in a bi-directional fashion to communicate the status of pathogen recognition to the brain and the immune response is influenced by physiological changes. The network of ligands and their receptors involved includes cytokines and chemokines, corticosteroids, classical pituitary hormones, catecholamines and neuropeptides (e.g. opioids), as well as neural pathways. We studied the role of opioid, adrenergic and melatonin G-protein coupled receptors (GPCR) on carp (Cyprinus carpio) leucocytes. Ligand interaction by morphine and adrenaline both in vitro and in vivo resulted in considerable decrease of chemotaxis and expression of CXC chemokines and chemokine CXC receptors. These effects may have substantial influence on the process of inflammation, the efficacy of which is crucial for an effective immune response. Both opioid receptors and chemokine receptors are G-protein coupled receptors (GPCRs), and were classically assumed to function as monomers. This paradigm is now challenged by the emerging concept of homo- and hetero dimerization which may represent the native form of many receptors. G-protein coupling, downstream signaling and regulatory processes such as receptor internalization are largely influenced by the dimeric nature. The true functional importance of GPCR interactions remains enigmatic, but it certainly has implications with respect to the specificity of currently used medications. This review focuses on the important function of chemokine GPCRs during inflammation and the potential neuroendocrine modulation of this process through "neuroendocrine" GPCRs.
神经内分泌系统和免疫系统以双向方式相互作用，将病原体识别的状态传递给大脑，而免疫反应则受到生理变化的影响。涉及的配体及其受体网络包括细胞因子和趋化因子、皮质类固醇、经典垂体激素、儿茶酚胺和神经肽（如阿片类物质）以及神经通路。我们研究了阿片受体、肾上腺素能受体和褪黑素 G 蛋白偶联受体 (GPCR) 在鲤鱼 (Cyprinus carpio) 白细胞中的作用。吗啡和肾上腺素的配体相互作用无论是在体外还是体内，都导致趋化性和 CXC 趋化因子和趋化因子 CXC 受体表达显著下降。这些影响可能对炎症过程产生重大影响，而炎症过程的疗效对于有效的免疫反应至关重要。阿片受体和趋化因子受体都是 G 蛋白偶联受体 (GPCR)，传统上被认为作为单体起作用。这一范式现在受到同源和异源二聚化新兴概念的挑战，这可能代表许多受体的天然形式。G 蛋白偶联、下游信号转导和受体内化等调节过程在很大程度上受到二聚体性质的影响。GPCR 相互作用的真正功能重要性仍然是个谜，但它肯定对当前使用的药物的特异性有影响。这篇综述重点介绍了趋化因子 GPCR 在炎症过程中的重要功能，以及通过“神经内分泌”GPCR 对这一过程的潜在神经内分泌调节。
