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Suppression of TNF-alpha-induced MMP-9 expression by a cell-permeable superoxide dismutase in keratinocytes  [2011]

Song, H.Y., Hallym University, Chuncheon, Republic of Korea Ju, S.M., Hallym University, Chuncheon, Republic of Korea Goh, A.R., Hallym University, Chuncheon, Republic of Korea Kwon, D.J., Hallym University, Chuncheon, Republic of Korea et al.

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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 gelatinolylic 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.

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Biochemistry and Molecular Biology reports

ISSN : 1976-6696

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