Becher E, Mahnke K, Brzoska T, Kalden D H, Grabbe S, Luger T A
Ludwig Boltzmann-Institut for Cell- and Immunobiology of the Skin, University of Münster, Germany.
Ann N Y Acad Sci. 1999 Oct 20;885:188-95. doi: 10.1111/j.1749-6632.1999.tb08676.x.
The neuropeptide, alpha-melanocyte-stimulating hormone (alpha-MSH) is well known for its immunomodulating capabilities. alpha-MSH antagonizes the activity of numerous proinflammatory mediators; for example, Interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha (TNF alpha), and bacterial endotoxin. In vivo alpha-MSH has been shown to suppress a contact hypersensitivity reaction in mice, and to induce hapten-specific tolerance. Since antigen presenting cells (APC) represent key elements for tolerance induction, the effect of alpha-MSH, and the expression of its receptor-melanocortin receptor-1 (MC-1R), on human peripheral blood-derived monocytes and dendritic cells (DC), was investigated. Semiquantitative RT-PCR demonstrated that monocytes and DC express MC-1R, but none of the other members of the MC-receptor family. Moreover, the extent of MC-1R expression correlated with the state of activation of these cells. Since the major ligand of MC-1R is alpha-MSH the question of whether alpha-MSH affects the function of monocyte derived DC was further investigated. We found that the expression of the costimulatory molecules CD 86 and CD 40 was downregulated on DC in the presence of alpha-MSH. Thus, alpha-MSH may exert its immunosuppressive effects by altering the function of APC.
神经肽α-黑素细胞刺激素（α-MSH）因其免疫调节能力而广为人知。α-MSH可拮抗多种促炎介质的活性；例如，白细胞介素-1（IL-1）、IL-6、肿瘤坏死因子α（TNFα）和细菌内毒素。在体内，α-MSH已被证明可抑制小鼠的接触性超敏反应，并诱导半抗原特异性耐受。由于抗原呈递细胞（APC）是诱导耐受的关键因素，因此研究了α-MSH及其受体黑素皮质素受体-1（MC-1R）对人外周血来源的单核细胞和树突状细胞（DC）的影响。半定量逆转录聚合酶链反应（RT-PCR）表明，单核细胞和DC表达MC-1R，但不表达MC受体家族的其他成员。此外，MC-1R的表达程度与这些细胞的活化状态相关。由于MC-1R的主要配体是α-MSH，因此进一步研究了α-MSH是否影响单核细胞衍生DC的功能。我们发现，在α-MSH存在的情况下，DC上共刺激分子CD 86和CD 40的表达下调。因此，α-MSH可能通过改变APC的功能发挥其免疫抑制作用。
