title: Suppression of TNF-alpha-induced MMP-9 expression by a cell-permeable superoxide dismutase in keratinocytes.
abstract: Up-regulation of selected matrix metalloproteinases (MMPs) such as MMP-9 contributes to inflammatory processes during the development of various skin diseases, such as atopic dermatitis. In this study, we examined the effect of a cell-permeable superoxide dismutase (Tat-SOD) on TNF-α-induced MMP-9 expression in human keratinocyte cells (HaCaT). When Tat-SOD was added to the culture medium of HaCaT cells, it rapidly entered the cells in dose- and time-dependent manners. Tat-SOD decreased TNF-α-induced reactive oxygen species (ROS) generation. Tat-SOD also inhibited TNF-α-induced NF-κB DNA binding activity. Treatment of HaCaT cells with Tat-SOD significantly inhibited TNF-α-induced mRNA and protein expression of MMP-9, as measured by RT-PCR and Western blot analysis. In addition, Tat-SOD suppressed TNF-α-induced gelatinolytic activity of MMP-9. Taken together, our results indicate that Tat-SOD can suppress TNF-α-induced MMP-9 expression via ROS-NF-κB-dependent mechanisms in keratinocytes, and therefore can be used as an immunomodulatory agent against inflammatory skin diseases related to oxidative stress.
authors.affiliation: Department of Biomedical Science, Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon, Korea.
authors.forename: Ha Yong
authors.initials: HY
authors.lastname: Song
authors.forename: Sung Mi
authors.initials: SM
authors.lastname: Ju
authors.forename: Ah Ra
authors.initials: AR
authors.lastname: Goh
authors.forename: Dong-Joo
authors.initials: DJ
authors.lastname: Kwon
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
mesh_terms: D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; D004247:DNA; D013482:Superoxide Dismutase; D020780:Matrix Metalloproteinase 9