title: Double-stranded RNA induces MMP-9 gene expression in HaCaT keratinocytes by tumor necrosis factor-α.
abstract: Viral double-stranded RNA (dsRNA) and its synthetic analog poly (I:C) are recognized via multiple pathways and induce the expression of genes related to inflammation. In the present study, we demonstrate that poly (I:C) specifically induced the expression of matrix metallo-proteinase-9 (MMP-9) in HaCaT keratinocytes. Studies using specific pharmacological inhibitors revealed the involvement of NF-κB, p38 MAPK, and PI-3K signal transduction pathways in poly (I:C)-induced MMP-9 gene expression. MMP-9 gene induction was sensitive toward treatment with the macrolide antibiotic bafilomycin A1, a vacuolar H(+)-ATPase inhibitor, and with the lysosomotropic agent chloroquine. However, cycloheximide treatment only partially blocked poly (I:C)-induced MMP-9 gene expression. Although HaCaT keratinocytes produce a number of cytokines and chemokines in response to poly (I:C), stimulation experiments revealed that exclusively TNFα strongly promoted MMP-9 gene expression. During the antiviral response MMP-9 expression may be of importance for the tissue injury phase.
authors.affiliation: Institute of Immunology, Helmholtz Centre for Infection Research, Inhoffenstr 7, D-38124 Braunschweig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Voss
authors.forename: Kirsten
authors.initials: K
authors.lastname: Gescher
authors.forename: Andreas
authors.initials: A
authors.lastname: Hensel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nacken
authors.forename: Claus
authors.initials: C
authors.lastname: Kerkhoff
mesh_terms: D002461:Cell Line, Transformed; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018942:Macrolides / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000276:immunology; D015398:Signal Transduction; D012867:Skin / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018942:Macrolides; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D014409:Tumor Necrosis Factor-alpha; C040929:bafilomycin A1; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D025262:Vacuolar Proton-Translocating ATPases; D011070:Poly I-C