Potential Involvement of the IL-6/STAT3/MMP12 Signaling Axis in DMSO-Mediated Anti-Fibrotic Effects in Experimental

Yukang Zhu1, Lei Xu1, Wei You2

  • 1Department of Nuclear Medicine, The First Hospital of Anhui University of Science and Technology; Anhui University of Science and Technology.

Insights

Dimethyl sulfoxide (DMSO) shows potential in treating silicosis by reducing lung inflammation and fibrosis. It works by inhibiting the IL-6/STAT3 pathway, which lowers MMP12 expression and alleviates disease symptoms in mice.

Area of Science:

  • Pulmonary Medicine
  • Toxicology
  • Molecular Biology

Background:

  • Silicosis is a serious lung disease caused by silica dust inhalation.
  • Current treatments for silicosis are limited, highlighting the need for novel therapeutic strategies.
  • Dimethyl sulfoxide (DMSO) has demonstrated anti-inflammatory properties in various contexts.

Purpose of the Study:

  • To investigate the anti-inflammatory and anti-fibrotic effects of DMSO in a mouse model of silicosis.
  • To explore the potential therapeutic value of DMSO for silicosis treatment.
  • To elucidate the molecular mechanisms underlying DMSO's effects on silicosis.

Main Methods:

  • A mouse model of silicosis was established via intranasal instillation of silica.
  • Mice were treated with DMSO via intraperitoneal injection for one month.
  • Lung tissues underwent transcriptomic analysis (limma), GO/KEGG enrichment (ClusterProfiler), histopathology (HE, Masson's trichrome), and Western blot.

Main Results:

  • DMSO treatment attenuated weight loss and reduced collagen deposition in silica-induced silicosis.
  • Transcriptomic analysis revealed suppressed fibrosis-related pathways and identified 51 key genes, including downregulated MMP12.
  • Western blot confirmed reduced MMP12, IL-6, and p-STAT3 levels, indicating inhibition of the IL-6/STAT3 signaling pathway.

Conclusions:

  • DMSO alleviates pulmonary fibrosis in silicosis by modulating the IL-6/STAT3-MMP12 signaling axis.
  • DMSO demonstrates therapeutic potential for silicosis by inhibiting inflammation and fibrosis.
  • Targeting the IL-6/STAT3 pathway represents a promising therapeutic strategy for silicosis.