Cytokine Neuropeptide Interactions in the Skin
There is clear evidence that there is a close relationship between immunoregulatory cytokines which have recently been demonstrated to be synthesized and released by epidermal cells and pituitary-derived neuropeptides such as adrenocorticotropin (ACTH) and melanocyte stimulating hormone (aMSH). Therefore, it was investigated whether keratinocytes are capable of producing neuropeptides. Supernatant fluids derived from normal human keratinocytes and from epidermoid carcinoma cell lines (A431, KB) contained significant levels of both aMSH and ACTH. Northern blot analysis using a cDNA probe for the αMSH/ACTH precursor, proopiomelanocortin (POMC), revealed the expression of POMC specific mRNA in normal keratinocytes as well as in epidermoid carcinoma cell lines. The production of αMSH as well as ACTH was significantly upregulated, at both the protein and mRNA level, after stimulation with the tumor promoters, phorbol myristate acetate (PMA) or ultraviolet (UV) light, or with interleukin-1 (IL-1). Since it has recently been shown that αMSH exhibits immunomodulatory capacities, the effect of αMSH on MHC class I and class II as well as on ICAM-1 expression was investigated. aMSH (10-9M) antigen significantly blocked MHC class I expession on peripheral blood mononuclear cells, cells from a monomyelocytic cell line (U937) and A431 cells, but MHC class II antigen and ICAM-1 expression were not affected. These data indicate that keratinocytes, in addition to cytokines, produce neuropeptides which also appear to function as regulatory elements of the skin immune system.
KeywordsA431 Cell Phorbol Myristate Acetetate Corticotropin Release Hormone Phorbol Myristate Acetate Normal Human Keratinocytes
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