Abstract
Melanocortin peptides, the collective term for α-, β-, and γ-melanocyte-stimulating hormone (α-, β-, γ-MSH) and adrenocorticotropic hormone (ACTH), are elements of an ancient modulatory system. Natural melanocortins derive from the common precursor pro-opiomelanocortin (POMC). Five receptor subtypes for melanocortins (MC1-MC5) are widely distributed in brain regions and in peripheral cells. Melanocortin receptor activation by natural or synthetic ligands exerts marked anti-inflammatory and immunomodulatory effects. The anticytokine action and the inhibitory influences on inflammatory cell migration make melanocortins potential new drugs for treatment of inflammatory disorders. Effectiveness in treatment of acute, chronic, and systemic inflammatory disorders is well documented in preclinical studies. Further, melanocortins are promising compounds in neuroprotection. This review examines the main signaling circuits in anti-inflammatory and immunomodulatory actions of melanocortins, and the potential therapeutic use of these molecules.
Keywords: α-, β-, and γ-melanocyte-stimulating hormone (α-, β-, γ-MSH), acute respiratory distress syndrome (ARDS), adhesion molecules, adrenocorticotropic hormone (ACTH), allergic inflammation, brain injury, cyclic 3’, , cytokines, endothelial cells, fibroblast, G protein-coupled receptors (GPCRs), gout, inflammatory bowel disease (IBD), keratinocyte, lymphocyte, macrophage, melanocortin receptors, melanocortin receptor accessory protein (MRAP), melanocyte, monocyte, neutrophil, neuroprotection, nuclear factor κB (NF-κB), pro-opiomelanocortin (POMC), reperfusion injury, rheumatoid arthritis, septic shock, signal transducers and activator of transcription (STAT), suppressors of cytokine signaling (SOCS), tumor necrosis factor α (TNF-α)