Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2/STAT3 signaling pathways
Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic so far. Pirfenidone has consistently been shown to have anti-inflammatory and anti-fibrotic effects, but the specific mechanism by...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S014765132200906X |
| _version_ | 1798000585750872064 |
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| author | Qiong Tang Chen Xing Ming Li Qiang Jia Cunxiang Bo Zhenling Zhang |
| author_facet | Qiong Tang Chen Xing Ming Li Qiang Jia Cunxiang Bo Zhenling Zhang |
| author_sort | Qiong Tang |
| collection | DOAJ |
| description | Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic so far. Pirfenidone has consistently been shown to have anti-inflammatory and anti-fibrotic effects, but the specific mechanism by which it ameliorates fibrosis in silicosis is unclear. A rat silicosis model was established in this study, and lung tissues and serum were collected by batch execution at 14, 28, and 56 days. Also, the effects of Pirfenidone on macrophage polarization and pulmonary fibrosis were evaluated in silicosis with early intervention and late treatment by histological examination, Enzyme-linked immunosorbent assay, Hydroxyproline assay, Western blot and Quantitative reverse transcription polymerase chain reaction. The results showed that Pirfenidone significantly reduced pulmonary fibrosis in rats with silicosis, and both early intervention and late treatment effectively inhibited the expression of α-SMA, Col-I, Vimentin, Hydroxyproline, IL-1β, IL-18, and the M2 macrophage marker CD206 and Arg-1, while only early intervention effectively inhibited E-cad, TGF-β1, TNF-α, and the M1 macrophage marker iNOS, CD86. Furthermore, Pirfenidone dramatically reduced the mRNA expression of the JAK2/STAT3. These findings imply that Pirfenidone may reduce pulmonary fibrosis in silicosis rats by inhibiting macrophage polarization via the JAK2/STAT3 signaling pathway. |
| first_indexed | 2024-04-11T11:22:41Z |
| format | Article |
| id | doaj.art-68f0ceb97b40460c8575516b5850d4ed |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-11T11:22:41Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-68f0ceb97b40460c8575516b5850d4ed2022-12-22T04:26:40ZengElsevierEcotoxicology and Environmental Safety0147-65132022-10-01244114066Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2/STAT3 signaling pathwaysQiong Tang0Chen Xing1Ming Li2Qiang Jia3Cunxiang Bo4Zhenling Zhang5Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250000, China; Shandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong 250000, ChinaJinan Center For Disease Control And Prevention, Jinan, Shandong 250000, ChinaShandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong 250000, ChinaShandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong 250000, ChinaShandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong 250000, China; Corresponding authors.Shandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong 250000, China; Corresponding authors.Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic so far. Pirfenidone has consistently been shown to have anti-inflammatory and anti-fibrotic effects, but the specific mechanism by which it ameliorates fibrosis in silicosis is unclear. A rat silicosis model was established in this study, and lung tissues and serum were collected by batch execution at 14, 28, and 56 days. Also, the effects of Pirfenidone on macrophage polarization and pulmonary fibrosis were evaluated in silicosis with early intervention and late treatment by histological examination, Enzyme-linked immunosorbent assay, Hydroxyproline assay, Western blot and Quantitative reverse transcription polymerase chain reaction. The results showed that Pirfenidone significantly reduced pulmonary fibrosis in rats with silicosis, and both early intervention and late treatment effectively inhibited the expression of α-SMA, Col-I, Vimentin, Hydroxyproline, IL-1β, IL-18, and the M2 macrophage marker CD206 and Arg-1, while only early intervention effectively inhibited E-cad, TGF-β1, TNF-α, and the M1 macrophage marker iNOS, CD86. Furthermore, Pirfenidone dramatically reduced the mRNA expression of the JAK2/STAT3. These findings imply that Pirfenidone may reduce pulmonary fibrosis in silicosis rats by inhibiting macrophage polarization via the JAK2/STAT3 signaling pathway.http://www.sciencedirect.com/science/article/pii/S014765132200906XPirfenidoneMacrophage polarizationSilicosisPulmonary fibrosisJAK2/STAT3 |
| spellingShingle | Qiong Tang Chen Xing Ming Li Qiang Jia Cunxiang Bo Zhenling Zhang Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2/STAT3 signaling pathways Ecotoxicology and Environmental Safety Pirfenidone Macrophage polarization Silicosis Pulmonary fibrosis JAK2/STAT3 |
| title | Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2/STAT3 signaling pathways |
| title_full | Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2/STAT3 signaling pathways |
| title_fullStr | Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2/STAT3 signaling pathways |
| title_full_unstemmed | Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2/STAT3 signaling pathways |
| title_short | Pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and JAK2/STAT3 signaling pathways |
| title_sort | pirfenidone ameliorates pulmonary inflammation and fibrosis in a rat silicosis model by inhibiting macrophage polarization and jak2 stat3 signaling pathways |
| topic | Pirfenidone Macrophage polarization Silicosis Pulmonary fibrosis JAK2/STAT3 |
| url | http://www.sciencedirect.com/science/article/pii/S014765132200906X |
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