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-Melanocyte Stimulating Hormone1
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
The proopiomelanocortin (POMC)-derived neuropeptide 
-melanocyte
stimulating hormone (-MSH) is known to modulate some aspects of
inflammation through direct effects on T cells, B cells, and monocytes.
To determine whether -MSH might similarly influence mast cell
responsiveness, mast cells were examined to see if they expressed the
receptor for -MSH, melanocortin-1 (MC-1), and whether -MSH
altered mast cell function. We thus first identified MC-1 on bone
marrow cultured murine mast cells (BMCMC) and a murine mast cell line
(MCP-5) employing flow cytometry and through detection of specific
binding. Subsequent treatment of mast cells with -MSH increased the
cAMP concentration in a characteristic biphasic pattern, demonstrating
that -MSH could affect intracellular processes. We next examined the
effect of -MSH on mediator release and cytokine expression.
IgE/DNP-human serum albumin-stimulated histamine release from mast
cells was inhibited by 
60% in the presence of -MSH. Although
activation of BMCMC induced the expression of mRNAs for the
inflammatory cytokines IL-1ß, IL-4, IL-6, TNF-, and the chemokine
lymphotactin, mRNAs for IL-1ß, TNF-, and lymphotactin were
down-modulated in the presence of -MSH. Finally, IL-3-dependent
proliferative activity of BMCMC was slightly but significantly
augmented by -MSH. Taken together, these observations suggest that
-MSH may exert an inhibitory effect on the mast cell-dependent
component of a specific inflammatory response.
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