title: Regulated proenkephalin expression in human skin and cultured skin cells.
abstract: Skin responds to environmental stressors via coordinated actions of the local neuroimmunoendocrine system. Although some of these responses involve opioid receptors, little is known about cutaneous proenkephalin expression, its environmental regulation, and alterations in pathology. The objective of this study was to assess regulated expression of proenkephalin in normal and pathological skin and in isolated melanocytes, keratinocytes, fibroblasts, and melanoma cells. The proenkephalin gene and protein were expressed in skin and cultured cells, with significant expression in fibroblasts and keratinocytes. Mass spectroscopy confirmed Leu- and Met-enkephalin in skin. UVR, Toll-like receptor (TLR)4, and TLR2 agonists stimulated proenkephalin gene expression in melanocytes and keratinocytes in a time- and dose-dependent manner. In situ Met/Leu-enkephalin peptides were expressed in differentiating keratinocytes of the epidermis in the outer root sheath of the hair follicle, in myoepithelial cells of the eccrine gland, and in the basement membrane/basal lamina separating epithelial and mesenchymal components. Met/Leu-enkephalin expression was altered in pathological skin, increasing in psoriasis and decreasing in melanocytic tumors. Not only does human skin express proenkephalin, but this expression is upregulated by stressful stimuli and can be altered by pathological conditions.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA. aslominski@uthsc.edu
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Slominski
authors.forename: Michal A
authors.initials: MA
authors.lastname: Zmijewski
authors.forename: Blazej
authors.initials: B
authors.lastname: Zbytek
authors.forename: Anna A
authors.initials: AA
authors.lastname: Brozyna
authors.forename: Jackie
authors.initials: J
authors.lastname: Granese
authors.forename: Alexander
authors.initials: A
authors.lastname: Pisarchik
authors.forename: Andre
authors.initials: A
authors.lastname: Szczesniewski
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Tobin
mesh_terms: D002478:Cells, Cultured; D004743:Enkephalin, Leucine / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D011498:Protein Precursors / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000819:agonists; D051197:Toll-Like Receptor 4 / Q000819:agonists
chemical_list: D004745:Enkephalins; D055666:Lipopeptides; D008070:Lipopolysaccharides; C508075:Pam(3)CSK(4) peptide; D011498:Protein Precursors; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C029992:proenkephalin; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine