The role of alpha-MSH as a modulator of cutaneous inflammation.
Among various neuropeptides such as substance P, calcitonin gene-related peptide and others, alpha-melanocyte-stimulating hormone (alpha-MSH) was found to be produced in the skin. Moreover, melanocortin receptor 1 (MC-1R), which is specific for alpha-MSH and ACTH, is expressed in the skin on keratinocytes, dendritic cells, macrophages and endothelial cells. In monocytes, macrophages and dendritic cells alpha-MSH inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL-2, IFN-gamma, TNF-alpha and IL-1. It downregulates the expression of costimulatory molecules such as CD86 and CD40 and induces the production of suppressor factors such as the cytokine synthesis inhibitory factor IL-10. On endothelial cells alpha-MSH is capable of downregulating the LPS-induced expression of adhesion molecules such as vascular cell adhesion molecule (VCAM) and E-selectin. Moreover, the LPS-induced activation of transcription factors such as NF kappa B is downregulated by alpha-MSH. In a mouse model i.v. or topical application of alpha-MSH was found to inhibit the induction phase as well as the effector phase of contact hypersensitivity (CHS) reactions and to induce hapten-specific tolerance. These findings indicate that the production of immunosuppressing neuropeptides such as alpha-MSH by epidermal cells may play an essential role during the pathogenesis of immune and inflammatory reactions in the skin.
Luger
T A
TA
Department of Dermatology, Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Münster, Münster, Germany. luger@uni-muenster.de
Brzoska
T
T
Scholzen
T E
TE
Kalden
D H
DH
Sunderkötter
C
C
Armstrong
C
C
Ansel
J
J
D000818:Animals; D006801:Humans; D007249:Inflammation; D015213:Neuroimmunomodulation; D018043:Receptors, Corticotropin / Q000276:immunology; D044101:Receptors, Melanocortin; D012871:Skin Diseases / Q000276:immunology*; D000521:alpha-MSH / Q000276:immunology*
D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D000521:alpha-MSH