KMID : 0624620110440070462
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BMB Reports 2011 Volume.44 No. 7 p.462 ~ p.467
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Suppression of TNF-alpha-induced MMP-9 expression by a cell-permeable superoxide dismutase in keratinocytes
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Song Ha-Yong
Ju Sung-Mi Goh Ah-Ra Kwon Dong-Joo Choi Soo-Young Park Jin-Seu
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Abstract
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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-¥á-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-¥á-induced reactive oxygen species (ROS) generation. Tat-SOD also inhibited TNF-¥á-induced NF-¥êB DNA binding activity. Treatment of HaCaT cells with Tat-SOD significantly inhibited TNF-¥á-induced mRNA and protein expression of MMP-9, as measured by RT-PCR and Western blot analysis. In addition, Tat-SOD suppressed TNF-¥á-induced gelatinolytic activity of MMP-9. Taken together, our results indicate that Tat-SOD can suppress TNF-¥á-induced MMP-9 expression via ROS-NF-¥êB-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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KEYWORD
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Inflammation, Keratinocyte, MMP-9, NF-¥êB, SOD, TNF-¥á
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