title: Ultraviolet irradiation increases matrix metalloproteinase-8 protein in human skin in vivo.
abstract: Humans express three distinct collagenases, MMP-1, MMP-8, and MMP-13, that initiate degradation of fibrillar type I collagen. We have previously reported that ultraviolet irradiation causes increased expression of MMP-1, but not MMP-13, in keratinocytes and fibroblasts in human skin in vivo. We report here that ultraviolet irradiation increases expression of MMP-8 in human skin in vivo. Western analysis revealed that levels of the full-length, 85 kDa proenzyme form of MMP-8 increased significantly within 8 h post ultraviolet irradiation (2 minimal erythema doses). Increased full-length MMP-8 protein was associated with infiltration into the skin of neutrophils, which are the major cell type that expresses MMP-8. Immunofluorescence revealed coexpression of MMP-8 and neutrophil elastase, a marker for neutrophils. Immunohistology demonstrated MMP-8 expression in neutrophils in the papillary dermis between 4 and 8 h post ultraviolet irradiation, and in the epidermis at 24 h post radiation. MMP-8 mRNA expression was not detected in nonirradiated or ultraviolet-irradiated human skin, indicating that increased MMP-8 following ultraviolet irradiation resulted from preexisting MMP-8 protein in infiltrating neutrophils. Pretreatment of skin with the glucocorticoid clobetasol, but not all-trans retinoic acid, significantly blocked ultraviolet-induced increases in MMP-8 protein levels, and neutrophil infiltration. In contrast, all-trans retinoic acid and clobetasol were equally effective in blocking ultraviolet induction of MMP-1 and degradation of collagen in human skin in vivo. Taken together, these data demonstrate that ultraviolet irradiation increases MMP-8 protein, which exists predominantly in a latent form within neutrophils, in human skin in vivo. Although ultraviolet irradiation induces both MMP-1 and MMP-8, ultraviolet-induced collagen degradation is initiated primarily by MMP-1, with little, if any, contribution by MMP-8.
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA. dianemch@umich.edu
authors.forename: G J
authors.initials: GJ
authors.lastname: Fisher
authors.forename: H C
authors.initials: HC
authors.lastname: Choi
authors.forename: Z
authors.initials: Z
authors.lastname: Bata-Csorgo
authors.forename: Y
authors.initials: Y
authors.lastname: Shao
authors.forename: S
authors.initials: S
authors.lastname: Datta
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.forename: J J
authors.initials: JJ
authors.lastname: Voorhees
mesh_terms: D000328:Adult; D001706:Biopsy; D002990:Clobetasol / Q000008:administration & dosage; D003094:Collagen / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007641:Keratolytic Agents / Q000008:administration & dosage; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology / Q000528:radiation effects; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000201:enzymology* / Q000473:pathology / Q000528:radiation effects*; D015595:Skin Aging / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D014212:Tretinoin / Q000008:administration & dosage; D014466:Ultraviolet Rays
chemical_list: D005938:Glucocorticoids; D007641:Keratolytic Agents; D012333:RNA, Messenger; D014212:Tretinoin; D003094:Collagen; D002990:Clobetasol; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1