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

Summary

This study suggests that dimethyl sulfoxide (DMSO) may alleviate silica-induced pulmonary inflammation and fibrosis in mice. Transcriptomic and experimental analyses suggest that its protective effects may involve suppression of the IL-6/STAT3 signaling pathway and downregulation of MMP12 expression, providing potential therapeutic insights for silicosis treatment.

Abstract

This study aims to investigate the anti-inflammatory and anti-fibrotic effects of dimethyl sulfoxide (DMSO) in a mouse model of silicosis, thereby exploring its potential therapeutic value.

A mouse model of silicosis was established by intranasal instillation, and DMSO treatment was administered via intraperitoneal injection. The experiment was conducted over a period of 1 month. Lung tissues were collected from all mice; a subset was subjected to transcriptomic analysis, and differentially expressed genes were identified using the limma package. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were conducted using ClusterProfiler to investigate gene functions and associated pathways. The remaining samples were subjected to histopathological assessment by hematoxylin and eosin staining (HE) and Masson’s trichrome staining, while Western blot analysis was performed to validate transcriptomic results.

This study suggests that DMSO may alleviate the fibrotic process in silicosis by modulating the IL-6/STAT3-MMP12 signaling axis. In the silica-induced silicosis mouse model, DMSO attenuated disease-associated weight loss and reduced collagen deposition. Transcriptomic analysis indicated that DMSO suppressed the activity of multiple fibrosis-related pathways and identified 51 key genes, including MMP12, which was significantly downregulated. Western blot analysis further confirmed reduced MMP12 expression, accompanied by markedly decreased levels of IL-6 and p-STAT3, suggesting the IL-6/STAT3 pathway may play a crucial role in regulating MMP12 expression.

DMSO may attenuate inflammatory responses and pulmonary fibrosis in silicosis by inhibiting activation of the IL-6/STAT3 signaling pathway, thereby reducing MMP12 expression.

Introduction

Silicosis is one of the major forms of occupational pneumoconiosis1, characterized by persistent pulmonary inflammation and irreversible pulmonary fibrosis resulting from prolonged exposure to silica dust^2,3. The pathogenesis of this silicosis is highly complex. Although previous studies have demonstrated that aberrant macrophage activation⁴, excessive proliferation of fibroblasts, epithelial-mesenchymal transition, and abnormal deposition of extracellular matrix (ECM) components are critical contributors to fibrotic development^5,6

Protocol

All animal experiments conducted in this study were approved by the Science and Technology Ethics Committee of Anhui University of Science and Technology (Approval No. GZ2025-048) and strictly adhered to the national standards for laboratory animal welfare (GB/T 35892-2018) of China. Figure 1 shows the study design.

Preparation of solutions​

Preparation of silica suspension:

Crystalline silica (SiO₂, 80%, particle size 1–5 µm) was sterilized by autoclaving. The sterile silica powder was then dispersed in sterile sali....

Results

DMSO alleviates silica-induced pulmonary fibrosis in mice (Figure 2)

To evaluate the effects of DMSO on pathological processes and lung tissue alterations in a silicosis model, four experimental groups were established (Figure 2A). Body weight changes were monitored over a 1-month period.

The results demonstrated that mice in the Silicosis group exhibited a continuous decli.......

Discussion

Silicosis remains one of the most severe occupational lung diseases worldwide, characterized by persistent inflammation and progressive pulmonary fibrosis, which substantially impair lung function and patient quality of life²⁵. In this study, using a silica-induced murine model, we systematically examine the potential protective effects of dimethyl sulfoxide (DMSO) during the early stage. The findings here suggest that DMSO treatment attenuates inflammatory cell infiltration and mitigates fibrotic.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
10% SDS-PAGE	Servicebio	G2177
BCA Protein Assay Kit	Servicebio	G2026
C57BL/6J mice	Changzhou Cavens Laboratory Animal Co., Ltd.	No: SCXY(Su)2011-0003
Crystalline silica	Sigma Aldrich	No.S5631
DMSO	Servicebio	GC203006
IL-6	Affinity Biosciences	DF6087
loading buffer	Bioteke	P0015L
MMP12	Servicebio	GB115475
p-STAT3	Servicebio	GB150001
RIPA lysis buffer	Servicebio	G2002
Secondary antibody	Servicebio	GB23303
skim milk	Servicebio	GC310001
STAT3	Servicebio	GB11176
β-Actin	Servicebio	GB11001