Cutaneous Immunomodulation and Coordination of Skin Stress Responses by α‐Melanocyte‐Stimulating Hormone^a

Abstract

The capacity of the skin immune system to mount various types of immune responses is largely dependent on their ability to release and respond to different signals provided by immunoregulatory mediators such as cytokines. There is recent evidence that neuropeptides such as alpha-melanocyte-stimulating hormone (alpha MSH), upon stimulation, are released by epidermal cells including keratinocytes, Langerhans cells, and melanocytes as well as immunocompetent cells. Moreover, alpha MSH recently has been recognized as a potent immunomodulating agent, which inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL-1, IL-2, interferon-gamma, downregulates the expression of costimulatory molecules (B7) on antigen-presenting cells; and recently turned out to be a potent inducer of inhibitory mediators such as cytokine synthesis inhibitory factor interleukin-10. Recently, it also was discovered that monocytes among the five known melanocortin (MC) receptors only express MC-1, which is specific for alpha MSH. The expression of MC-1 on monocytes is upregulated by mitogens, endotoxins, and proinflammatory cytokines. There is also recent evidence for the in vivo relevance of the immunosuppressing capacity of alpha MSH. Accordingly, in animals alpha MSH has been shown to inhibit the induction of contact hypersensitivity reactions and to induce hapten-specific tolerance. These findings indicate that, in addition to the cytokine network, neurohormones within the cutaneous microenvironment are a crucial element for the induction, elicitation, and regulation of cutaneous immune and inflammatory responses.

Identification of β‐endorphin, α‐MSH and ACTH peptides in cultured human melanocytes, melanoma and squamous cell carcinoma cells by RP‐HPLC

“…Recent results, including those from our laboratory, have documented that skin produces POMC (1)(2)(3)(4).…”

α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

“…Production of this neuropeptide has been reported following injury, UV light exposure, trauma, and infection (24). Increased production of ␣-MSH was measured in patients with psoriasis vulgaris and other cutaneous inflammatory conditions (13,14).…”

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

“…POMC peptides, originally discovered as pituitary hormones, have been detected in various tissues including the skin and are expressed by melanocytes, keratinocytes, adnexal epithelial cells, microvascular endothelial cells, Langerhans cells, mast cells, and fibroblasts as well as by immune cells such as monocytes and macrophages (496). The hair follicle therefore seems to generate the whole armada of mediators generated by the hypophysialadrenal (HPA) axis such as ␤-endorphin, MSH, ACTH, CRH, their receptors (-opioid receptor, MC-R, ACTH-R, CRH-R), and enzymes regulating POMC peptide function like PC1 and PC2 (367).…”