title: Matrix metalloproteinase-19 expression in normal and diseased skin: dysregulation by epidermal proliferation.
abstract: Most of the matrix metalloproteinases (MMP) are not expressed in normal intact skin but they are upregulated in inflamed or diseased skin. The recently cloned MMP-19 is one of the few MMP members that are also expressed in healthy epidermis. In this study, we found that MMP-19 is generally coexpressed with cytokeratin 14 that is confined to keratinocytes of the stratum basale. MMP-19 was also detected in hair follicles, sebaceous glands, and eccrine sweat glands. Its expression, however, changed in cutaneous diseases exhibiting increased alternations of epidermal proliferation, such as psoriasis, eczema, and tinea. In the affected area, MMP-19 was also found in suprabasal and spinous epidermal layers. We also studied the regulation of MMP-19 expression at the protein level, as well as by using a promoter assay. The constitutive expression of MMP-19 was upregulated with phorbol myristate acetate and downregulated with retinoic acid and dexamethasone. Tumor necrosis factor-alpha, interleukin (IL)-6, TGF-beta, IL-15, IL-8, and RANTES as well as the bacterial compounds lipopolysaccharide and lipoteichoic acid did not show any profound effect in HaCaT cells. In contrast, type IV and type I collagens upregulated MMP-19 significantly. The dysregulation of MMP-19 expression in epidermis suggests its possible involvement in the perpetuation of cutaneous infections and proliferative disorders such as psoriasis.
authors.affiliation: Institute of Biochemistry, University of Kiel, Kiel, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Sadowski
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dietrich
authors.forename: Matthias
authors.initials: M
authors.lastname: Müller
authors.forename: Blanka
authors.initials: B
authors.lastname: Havlickova
authors.forename: Michael
authors.initials: M
authors.lastname: Schunck
authors.forename: Ehrhardt
authors.initials: E
authors.lastname: Proksch
authors.forename: Markus Stefan
authors.initials: MS
authors.lastname: Müller
authors.forename: Radislav
authors.initials: R
authors.lastname: Sedlacek
mesh_terms: D001808:Blood Vessels / Q000201:enzymology; D002455:Cell Division; D002460:Cell Line; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology; D018859:Hair Follicle / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000201:enzymology; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic; D011565:Psoriasis / Q000201:enzymology; D012867:Skin / Q000201:enzymology*; D012871:Skin Diseases / Q000201:enzymology*
chemical_list: D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19