2. Academic Validation
  3. Iguratimod decreases bleomycin-induced pulmonary fibrosis in association with inhibition of TNF-α in mice

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

  • Int Immunopharmacol. 2021 Oct;99:107936. doi: 10.1016/j.intimp.2021.107936.
Siqi Shao 1,  Ziye Qu 1,  Yiwen Liang 2,  Yan Xu 2,  Dongmei Zhou 1,  Danhua Li 3,  Ying Zhang 4,  Songlou Yin 5
Affiliations

Affiliations

  • 1 Department of Rheumatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China; The First Clinical Medicine School, Xuzhou Medical University, Xuzhou 221002, China.
  • 2 Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221002, China.
  • 3 Department of Pathology, Laboratory of Clinical and Experimental Pathology, Xuzhou Medical University, Xuzhou 221004, China.
  • 4 Department of Pathology, Laboratory of Clinical and Experimental Pathology, Xuzhou Medical University, Xuzhou 221004, China. Electronic address: [email protected].
  • 5 Department of Rheumatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China; The First Clinical Medicine School, Xuzhou Medical University, Xuzhou 221002, China. Electronic address: [email protected].
PMID: 34284287 DOI: 10.1016/j.intimp.2021.107936
Abstract

Severe interstitial lung disease secondary to connective tissue diseases, characterized by pulmonary inflammation and fibrosis, often have very poor prognosis due to lack of effective treatments. Iguratimod (IGU) shows encouraging efficacy in treating connective tissue diseases, however, the underlying mechanism is still to be elucidated. In this study, we investigated the impact of IGU on bleomycin-induced interstitial lung disease and the related tumor necrosis factor-α (TNF-α) signaling pathway in mice and in the alveolar epithelial cell A549. We found IGU decreased pulmonary inflammation and fibrosis and expression of fibrosis-related genes such as Collagen I, α-smooth muscle actin (α-SMA) and matrix metalloproteinase-2 (MMP-2) induced by bleomycin. IGU inhibited epithelial-mesenchymal transition as evidenced by decreased E-cadherin expression but increased vimentin expression. IGU reduced TNF-α production in the pulmonary fibrosis murine model and in the in vitro cultured A549 cells. Furthermore, IGU ameliorated TNF-α-induced severe pulmonary fibrosis and inhibited TNF-α-induced activation of NF-κB. In addition, IGU decreased IL-6 production and phosphorylation of STAT3. In conclusion, the IGU-mediated anti-fibrogenesis effect was associated with the inhibition of TNF-α and NF-κB.

Keywords

Iguratimod; Pulmonary fibrosis; Tumor necrosis factor-α.

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