title: Alpha-melanocyte stimulating hormone induces collagenase/matrix metalloproteinase-1 in human dermal fibroblasts.
abstract: Recent reports have suggested that alpha-melanocyte stimulating hormone (alpha-MSH) plays an important role in untraviolet (UV) irradiation mediated skin changes including pigmentation, inflammation and connective tissue damage. alpha-MSH synthesis has been found to be induced in human keratinocytes following UV irradiation. In order to test the hypothesis whether UV induced alpha-MSH - via a paracrine loop - regulates the synthesis and the activity of collagenase/MMP-1, we studied the effects of alpha-MSH on the expression of MMP-1 and its tissue inhibitor of matrix metalloproteinases (TIMP-1). Confluent human dermal fibroblast cultures from foreskin biopsies of healthy human donors were treated with 10(-5)M, 10(-8)M and 10(-11)M alpha-MSH for 30 min. As determined by Northern blot analysis 10(-5)M and 10(-8)M alpha-MSH dose- and time-dependently induced steady state levels of MMP-1 mRNA up to 9-fold compared to untreated controls. TIMP-1 mRNA steady state levels were also slightly induced, however, the increased MMP-1/TIMP-1 ratio when normalized to beta-actin reflected an unbalanced synthesis. MMP-1 protein expression was studied with an immunofluorescence technique using a monoclonal antibody against MMP-1. After alpha-MSH treatment an increased number of fibroblasts revealed an intense perinuclear staining pattern compared to the less intense staining of control fibroblasts. The overall collagenolytic activity of supernatants from alpha-MSH treated fibroblasts was increased by 35%. Our data support the view that UV induced alpha-MSH - by the stimulation of collagenase/MMP-1 - may contribute to the loss of interstitial collagen related to cutaneous photoaging.
authors.affiliation: Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kiss
authors.forename: M
authors.initials: M
authors.lastname: Wlaschek
authors.forename: P
authors.initials: P
authors.lastname: Brenneisen
authors.forename: G
authors.initials: G
authors.lastname: Michel
authors.forename: C
authors.initials: C
authors.lastname: Hommel
authors.forename: T S
authors.initials: TS
authors.lastname: Lange
authors.forename: D
authors.initials: D
authors.lastname: Peus
authors.forename: L
authors.initials: L
authors.lastname: Kemeny
authors.forename: A
authors.initials: A
authors.lastname: Dobozy
authors.forename: K
authors.initials: K
authors.lastname: Scharffetter-Kochanek
mesh_terms: D002457:Cell Extracts / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005455:Fluorescent Antibody Technique; D006801:Humans; D006868:Hydrolysis; D020781:Matrix Metalloproteinase 1; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D002457:Cell Extracts; D012333:RNA, Messenger; D000521:alpha-MSH; D003094:Collagen; D017364:Collagenases; D020781:Matrix Metalloproteinase 1