Bhardwaj R S, Schwarz A, Becher E, Mahnke K, Aragane Y, Schwarz T, Luger T A
Ludwig Boltzmann Insitute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Münster, Germany.
J Immunol. 1996 Apr 1;156(7):2517-21.
There is strong evidence for the existence of a neuroimmune axis which is regulated by a network of interacting cytokines and neuropeptides. Accordingly, pro-opiomelanocortin-derived peptide hormones such as melanocyte-stimulating hormones (MSH), adrenocorticotropin, and beta-endorphin not only could be detected in many immunocompetent cells but also turned out to be potent immunomodulating and anti-inflammatory mediators, mainly through regulating cytokine production. Thus, it was investigated whether alpha-MSH, which is known to inhibit immune and inflammatory responses, would influence the production of the cytokine synthesis inhibitor IL-10 by human PBMC. Stimulation of PBMC with alpha-MSH resulted in a significantly enhanced release of, IL-10 protein. These data were confirmed by Northern blot analysis, which demonstrated increased IL-10 mRNA expression induced by alpha-MSH. This effect of alpha-MSH was dose-dependent; maximum IL-10 release and mRNA expression were obtained at a concentration of 10(-13) M. There is also clear evidence that only the C-terminal tripeptide of alpha-MSH was required to enhance IL-10 production. In addition, alpha-MSH and its tripeptide strongly induced IL-10 in purified monocytes. In contrast, neither unstimulated nor activated T lymphocytes produced increased amounts of IL-10 in response to alpha-MSH. These findings indicate that pro-opiomelanocortin peptides such as alpha-MSH are able to up-regulate the production of suppressor factors such as IL-10 in monocytes and thereby may contribute to immunosuppression.
有强有力的证据表明存在一个神经免疫轴，它由相互作用的细胞因子和神经肽网络调节。因此，源自阿片促黑激素原的肽类激素，如促黑素细胞激素（MSH）、促肾上腺皮质激素和β-内啡肽，不仅能在许多免疫活性细胞中检测到，而且还被证明是有效的免疫调节和抗炎介质，主要是通过调节细胞因子的产生。因此，人们研究了已知能抑制免疫和炎症反应的α-MSH是否会影响人外周血单核细胞（PBMC）中细胞因子合成抑制剂IL-10的产生。用α-MSH刺激PBMC导致IL-10蛋白的释放显著增强。这些数据通过Northern印迹分析得到证实，该分析表明α-MSH诱导了IL-10 mRNA表达增加。α-MSH的这种作用是剂量依赖性的；在10^(-13) M的浓度下获得了最大的IL-10释放和mRNA表达。也有明确的证据表明，仅α-MSH的C末端三肽就足以增强IL-10的产生。此外，α-MSH及其三肽在纯化的单核细胞中强烈诱导IL-10。相反，未刺激的或活化的T淋巴细胞在对α-MSH的反应中均未产生增加量的IL-10。这些发现表明，诸如α-MSH之类的阿片促黑激素原肽能够上调单核细胞中诸如IL-10等抑制因子的产生，从而可能有助于免疫抑制。
