Luger T A, Scholzen T, Grabbe S
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Münster, Germany.
J Investig Dermatol Symp Proc. 1997 Aug;2(1):87-93. doi: 10.1038/jidsymp.1997.17.
alpha-Melanocyte stimulating hormone is a neuroimmunomodulating peptide that was recently detected in many non-pituitary tissues including the skin. Accordingly, epidermal cells such as keratinocytes and melanocytes (as well as dermal cells such as fibroblasts and endothelial cells), after stimulation with pro-inflammatory cytokines or UV light, synthesize, and release alpha MSH. The effects of these peptides are mediated through specific melanocortin (MC) receptors that can be detected on immunocompetent and inflammatory cells as well as on keratinocytes, melanocytes, fibroblasts, and endothelial cells. In addition to its well known pigment-inducing capacity, alpha MSH is able to modulate keratinocyte proliferation and differentiation. Endothelial cell and fibroblast cytokine production and fibroblast collagenase production are also regulated by alpha MSH. The immunosuppressive capacity of alpha MSH is mediated mainly through its effects on monocyte and macrophage functions. Accordingly, alpha MSH downregulates the production of pro-inflammatory cytokines and accessory molecules on antigen-presenting cells. The production of suppressor factors such as IL-10, however, is upregulated by alpha MSH. The in vivo relevance of these data is documented by the finding that systemic application of alpha MSH inhibits the induction and the elicitation of murine contact hyper-sensitivity and induces hapten-specific tolerance. These findings indicate that alpha MSH is part of the mediator network that regulates cutaneous inflammation and hyper-proliferative skin diseases.
α-黑素细胞刺激素是一种神经免疫调节肽，最近在包括皮肤在内的许多非垂体组织中被检测到。因此，角质形成细胞和黑素细胞等表皮细胞（以及成纤维细胞和内皮细胞等真皮细胞）在受到促炎细胞因子或紫外线刺激后，会合成并释放α-MSH。这些肽的作用是通过特定的黑素皮质素（MC）受体介导的，这些受体可以在免疫活性细胞和炎症细胞以及角质形成细胞、黑素细胞、成纤维细胞和内皮细胞上检测到。除了其众所周知的诱导色素沉着的能力外，α-MSH还能够调节角质形成细胞的增殖和分化。α-MSH还可调节内皮细胞和成纤维细胞的细胞因子产生以及成纤维细胞胶原酶的产生。α-MSH的免疫抑制能力主要通过其对单核细胞和巨噬细胞功能的影响来介导。因此，α-MSH下调抗原呈递细胞上促炎细胞因子和辅助分子的产生。然而，α-MSH上调抑制因子如IL-10的产生。全身应用α-MSH可抑制小鼠接触性超敏反应的诱导和激发，并诱导半抗原特异性耐受，这一发现证明了这些数据在体内的相关性。这些发现表明，α-MSH是调节皮肤炎症和皮肤过度增殖性疾病的介质网络的一部分。
