Pro-opiomelanocortin-derived peptides induce IL-10 production in human monocytes.
Pro-opiomelanocortin-derived peptides induce IL-10 production in human monocytes.
复制标题
阿黑皮质素原衍生肽可诱导人单核细胞产生 IL-10。
作者：
R. Bhardwaj;A. Schwarz;E. Becher;K. Mahnke;Y. Aragane;T. Schwarz;T. Luger
有强有力的证据表明存在一个神经免疫轴，它是由相互作用的细胞因子和神经肽网络调节的。因此，促黑素细胞激素（melanoma cell -stimulating hormone， MSH）、促肾上腺皮质激素（adrenocorcotropin）和β -内啡肽（beta-endorphin）等促阿片黑素衍生的肽激素不仅在许多免疫能力细胞中检测到，而且主要通过调节细胞因子的产生，被证明是有效的免疫调节和抗炎介质。因此，我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PBMC产生细胞因子合成抑制剂IL-10。α - msh刺激PBMC可显著增强IL-10蛋白的释放。这些数据通过Northern blot分析证实，α - msh诱导IL-10 mRNA表达增加。α - msh的这种作用呈剂量依赖性；在浓度为10(-13)m时，IL-10的释放量和mRNA的表达量达到最大。同时也有明确的证据表明，只需要α - msh的c端三肽就可以促进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。相比之下，未受刺激的T淋巴细胞和活化的T淋巴细胞在α - msh的反应中都没有产生增加的IL-10。这些发现表明，α - msh等促阿皮质素肽能够上调单核细胞中IL-10等抑制因子的产生，从而可能有助于免疫抑制。
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.