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The Role of α‐MSH as a Modulator of Cutaneous Inflammation
Author(s) -
LUGER T. A.,
BRZOSKA T.,
SCHOLZEN T. E.,
KALDEN D.H.,
SUNDERKÖTTER C.,
ARMSTRONG C.,
ANSEL J.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb05388.x
Subject(s) - proinflammatory cytokine , cytokine , cell adhesion molecule , chemistry , microbiology and biotechnology , inflammation , immune system , endocrinology , biology , immunology
A bstract : Among various neuropeptides such as substance P, calcitonin gene‐related peptide and others, α‐melanocyte‐stimulating hormone (α‐MSH) was found to be produced in the skin. Moreover, melanocortin receptor 1 (MC‐1R), which is specific for α‐MSH and ACTH, is expressed in the skin on keratinocytes, dendritic cells, macrophages and endothelial cells. In monocytes, macrophages and dendritic cells α‐MSH inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL‐2, IFN‐γ, TNF‐α, 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 α‐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 NFκB is downregulated by α‐MSH. In a mouse model i.v. or topical application of α‐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 α‐MSH by epidermal cells may play an essential role during the pathogenesis of immune and inflammatory reactions in the skin.