Iguratimod decreases bleomycin-induced pulmonary fibrosis in association with inhibition of TNF-α in mice

doi:10.3877/cma.j.issn.1674-6902.2022.03.009

Abstract

Abstract:

Objective

To investigate the impact of iguratimod (IGU) on bleomycin-induced interstitial lung disease and the related tumor necrosis factor-α (TNF-α) signaling pathway in mice to explored the effectiveness and possible mechanism of IGU in treating ILD.

Methods

Construction ILD model. C57/BL6 mice were randomly divided into 5 groups: Normal group, BLM group, BLM+ IGU group, BLM+ TNF-α group, BLM+ TNF-α+ IGU group. After the model was established, mice reveived 0.5% CMC-Na or IGU (90 mg/kg, gavage). Some BLM-treated mice were injected intra-peritoneally with PBS or recombinant murine TNF-α (200 ng per mouse) twice a week. The mice were sacrificed at day 28. Observe the change of body weight. Observe the pathological changes of lung tissue by Masson staining. Western blot was used to detect protein levels of related markers.

Results

Compared with the BLM group, the weight of the mice in BLM+ TNF-α group decreased (P<0.05), and the weight of mice in IGU treatment group higher than in BLM+ TNF-α group (P<0.05). Compared with the BLM group, Masson staining indicated increased collagen deposition increased in BLM+ TNF-α group (P<0.05), while collagen deposition in BLM+ TNF-α+ IGU group decreased compared with BLM+ TNF-α group (P<0.05). Compared with the BLM group, the protein levels of α-SMA, MMP-2, and Vimentin in the BLM+ TNF-α group increased, but E-cadherin protein level decreased (P<0.05), which were reversed by concurrent use of IGU (P<0.05).

Conclusion

IGU can regulate inflammation by inhibiting of TNF-α and EMT, and relieve interstitial lung disease caused by bleomycin.

Key words: Iguratimod, Interstitial lung disease, Tumor necrosis factor-α, Epithelial mesenchymal transformation

Xinnuo Cai, Siqi Shao, Hua Ma, Dongmei Zhou, Bin Pan, Songlou Yin. Iguratimod decreases bleomycin-induced pulmonary fibrosis in association with inhibition of TNF-α in mice[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2022, 15(03): 331-334.

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