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

Ha Yong Song1, Sung Mi Ju, Ah Ra Goh

  • 1Department of Biomedical Science, Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon, Korea.

BMB Reports
|July 23, 2011
PubMed

Insights

Superoxide dismutase (SOD) derivative, Tat-SOD, reduces inflammatory skin disease markers. This study shows Tat-SOD inhibits matrix metalloproteinase-9 (MMP-9) expression by targeting reactive oxygen species (ROS) and NF-κB pathways in skin cells.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Immunology

Background:

  • Matrix metalloproteinases (MMPs), particularly MMP-9, are implicated in skin inflammation, including atopic dermatitis.
  • Tumor necrosis factor-alpha (TNF-α) triggers inflammatory responses in skin cells.

Purpose of the Study:

  • To investigate the effect of cell-permeable superoxide dismutase (Tat-SOD) on TNF-α-induced MMP-9 expression in HaCaT keratinocytes.
  • To elucidate the underlying mechanisms of Tat-SOD's action.

Main Methods:

  • HaCaT cells were treated with Tat-SOD and TNF-α.
  • Reactive oxygen species (ROS) generation was measured.
  • Nuclear factor-kappa B (NF-κB) DNA binding activity was assessed.
  • MMP-9 mRNA and protein expression were quantified using RT-PCR and Western blot.
  • MMP-9 gelatinolytic activity was analyzed.

Main Results:

  • Tat-SOD effectively penetrated HaCaT cells in a dose- and time-dependent manner.
  • Tat-SOD significantly reduced TNF-α-induced ROS generation and NF-κB DNA binding activity.
  • Tat-SOD suppressed TNF-α-induced MMP-9 mRNA and protein expression.
  • Tat-SOD inhibited the gelatinolytic activity of MMP-9.

Conclusions:

  • Tat-SOD effectively suppresses TNF-α-induced MMP-9 expression in keratinocytes.
  • The mechanism involves the downregulation of ROS and NF-κB signaling pathways.
  • Tat-SOD shows potential as an immunomodulatory agent for inflammatory skin conditions associated with oxidative stress.

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