Dimethyl sulfoxide attenuates TNF-α-induced production of MMP-9 in human keratinocytes

Area of Science:

• Dermatology
• Biochemistry
• Molecular Biology

Background:

• Dimethyl sulfoxide (DMSO) is a topical agent with antioxidant properties beneficial for chronic wound treatment.
• The impact of DMSO on matrix metalloproteinase-9 (MMP-9) in inflammatory wound healing remains unexplored.
• MMP-9 plays a critical role in tissue remodeling and can contribute to disordered healing.

Purpose of the Study:

• To investigate the potential of DMSO to attenuate tumor necrosis factor-alpha (TNF-α)-induced MMP-9 production and gene expression in human keratinocytes (HaCaT cells).
• To determine if DMSO can mitigate the effects of inflammation on MMP-9 activity in a cellular model relevant to wound healing.

Main Methods:

• Human keratinocytes (HaCaT) were treated with varying concentrations of DMSO (0.1-1%) for 24 hours.
• Cells were subsequently stimulated with tumor necrosis factor-alpha (TNF-α) (10 ng/ml) for another 24 hours.
• MMP-9 production was assessed using gelatin zymography, and MMP-9 mRNA expression was quantified via reverse transcription polymerase chain reaction (RT-PCR).

Main Results:

• DMSO significantly inhibited both MMP-9 protein levels and MMP-9 mRNA expression in TNF-α-stimulated HaCaT cells in a dose-dependent manner.
• Statistically significant inhibition of MMP-9 levels was observed at DMSO concentrations of 0.75% and higher.
• DMSO markedly reduced the TNF-α-induced increase in MMP-9 mRNA expression, suggesting transcriptional downregulation.

Conclusions:

• DMSO demonstrates the ability to attenuate TNF-α-induced MMP-9 production and gene expression in keratinocytes.
• The findings suggest DMSO acts by downregulating MMP-9 at the transcriptional level.
• DMSO may serve as a valuable therapeutic strategy to control excessive proteolytic activity in inflammatory skin conditions and promote effective wound healing.