Dimethyl Sulfoxide Attenuates TNF-α-Induced Production of MMP-9 in Human Keratinocytes

Abstract

Dimethyl sulfoxide (DMSO), an aprotic solvent, is found to be useful as a topical agent with antioxidant effects in treatment of chronic wounds. However, the effects of DMSO on matrix metalloproteinase-9 (MMP-9) production in the presence of an inflammatory environment as in the case of disordered wound healing has not been previously investigated. The aim of this study was to investigate whether TNF-α-induced MMP-9 levels and MMP-9 mRNA expression from human keratinocytes (HaCaT) might be attenuated by DMSO. Human keratinocytes were treated with DMSO (0.1–1%) for 24 h and then exposed to tumor necrosis factor (TNF)-α (10 ng/ml) for an additional 24 h. Expression and production of MMP-9 from HaCaT cells were determined by reverse transcription polymerase chain reaction (RT-PCR) and gelatin zymography, respectively. Results showed that DMSO inhibited production of both MMP-9 levels and MMP-9 mRNA expression in TNF-α-stimulated cells in a concentration-dependent manner. Inhibition of MMP-9 levels was statistically significant at DMSO concentrations of 0.75% and higher. Similarly, the increase of MMP-9 mRNA expression levels in TNF-α-stimulated cells was markedly reduced by DMSO. Data suggest that DMSO may attenuate the deleterious effects of MMP-9 through downregulation at the transcription level. Therefore, DMSO may provide a good strategy to prevent TNF-α-induced proteolytic activity in cutaneous inflammatory reactions.

Acknowledgments

This work was supported by the Scientific Grant Agency of the Ministry of Education of Slovak Republic and the Slovak Academy of Sciences, VEGA 2/0057/11.