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Stattic alleviates pulmonary fibrosis in a mouse model of rheumatoid arthritis-relevant interstitial lung disease.
- Source :
-
Experimental biology and medicine (Maywood, N.J.) [Exp Biol Med (Maywood)] 2023 Apr; Vol. 248 (8), pp. 712-721. Date of Electronic Publication: 2023 Mar 20. - Publication Year :
- 2023
-
Abstract
- Approximately 20% of rheumatoid arthritis (RA) patients have RA-related interstitial lung disease (RA-ILD). Stattic, an STAT3 inhibitor, has been confirmed to be relevant to both RA and ILD. Therefore, this study explored the effect of Stattic on the progression of joint disease and pulmonary fibrosis in zymosan-treated female SKG mice, an established model for autoimmune arthritis. The experimental mice developed pulmonary interstitial pneumonia, which is similar to human cellular and fibrotic nonspecific interstitial pneumonia. Oral gavage of Stattic (60 mg/kg/d) was initiated 10 weeks after zymosan injection. Arthritis and lung fibrosis outcome scores decreased significantly following Stattic treatment. An obvious decrease in lung collagen levels, measured using hydroxyproline level determination and collagen staining, was detected after 6 weeks in Stattic-exposed mice with established disease. Stattic also dramatically restricted arthritis progression, based on joint evaluation. Transforming growth factor beta 1 (TGF-β1) is a pivotal fibrosis-causing cytokine, used here to treat myofibroblasts, thereby establishing a lung fibrosis cell model. Stattic treatment can mitigate the TGF-β1-triggered inflammatory response, myofibroblast activation, oxidative stress, and hyperproliferation by modulating the JAK1/STAT3 pathway. Our observations support a direct role of Stattic-inhibited STAT3 activation in lung fibrosis, which may be particularly relevant in the RA-ILD context.
- Subjects :
- Female
Animals
Mice
Cyclic S-Oxides pharmacology
Cyclic S-Oxides therapeutic use
Disease Models, Animal
Bone Density drug effects
Cell Proliferation drug effects
Apoptosis drug effects
Transforming Growth Factor beta1 pharmacology
Idiopathic Pulmonary Fibrosis drug therapy
Idiopathic Pulmonary Fibrosis etiology
Idiopathic Pulmonary Fibrosis pathology
Arthritis, Rheumatoid complications
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3699
- Volume :
- 248
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Experimental biology and medicine (Maywood, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 36941782
- Full Text :
- https://doi.org/10.1177/15353702231157934