Colchicine alleviates interstitial lung disease in mice with experimental autoimmune myositis by inhibiting the formation of neutrophil extracellular traps
Abstract Background:Our previous study has shown that neutrophil extracellular traps (NETs) are associated with idiopathic inflammatory myopathy and its related interstitial lung disease (IIM-ILD). Colchicine plays an anti-inflammatory role mainly by inhibiting the activity and chemotaxis of neutrophils. This study will verify the role and mechanism of colchicine in IIM-ILD. Methods: A mouse model of experimental autoimmune myositis was established and divided into model group, colchicine treatment group (1, 2mg/kg), and healthy control group (n=5/ group). After 5 weeks, the mice were sacrificed to evaluate the degree of pulmonary interstitial lesions and the formation of NETs. Human neutrophils were stimulated with PMA in vitro, and the treatment group was pretreated with colchicine (40nmol/L). After 4 hours of culture, the neutrophils were stained with Sytox Green and observed by fluorescence microscopy. Human pulmonary microvascular endothelial cells were stimulated with NETs, and the experimental group was pretreated with colchicine (7.5, 15nmol/L), and the markers of inflammation and pyroptosis were detected 24h later. Results: (1) Pathological staining of lung tissue showed that colchicine treatment significantly alleviated interstitial lung disease in EAM mice. (2) After colchicine treatment, the infiltration of NETs in the lung tissue of EAM was significantly reduced, and the serum level of NETs was also significantly decreased (F=6.859, P < 0.05). (3) Colchicine intervention significantly attenuated the formation of NETs on neutrophils induced by PMA in vitro. (4) Colchicine significantly decreased the expression of inflammasomes and pyroptosis markers in NETs-stimulated human lung microvascular endothelial cells, and inhibited the production of inflammasomes and pyroptosis in the lung tissue of EAM in vivo. Conclusions: Colchicine can alleviate interstitial lung disease in EAM mice by inhibiting NETs formation, inflammasome activation and endothelial cell pyroptosis. These findings provide a basis for targeting NETs in the treatment of myositis-associated interstitial lung disease..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 21. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Feifei [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-4069157/v1 |
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| PPN (Katalog-ID): |
XRA043008844 |
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| 245 | 1 | 0 | |a Colchicine alleviates interstitial lung disease in mice with experimental autoimmune myositis by inhibiting the formation of neutrophil extracellular traps |
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| 520 | |a Abstract Background:Our previous study has shown that neutrophil extracellular traps (NETs) are associated with idiopathic inflammatory myopathy and its related interstitial lung disease (IIM-ILD). Colchicine plays an anti-inflammatory role mainly by inhibiting the activity and chemotaxis of neutrophils. This study will verify the role and mechanism of colchicine in IIM-ILD. Methods: A mouse model of experimental autoimmune myositis was established and divided into model group, colchicine treatment group (1, 2mg/kg), and healthy control group (n=5/ group). After 5 weeks, the mice were sacrificed to evaluate the degree of pulmonary interstitial lesions and the formation of NETs. Human neutrophils were stimulated with PMA in vitro, and the treatment group was pretreated with colchicine (40nmol/L). After 4 hours of culture, the neutrophils were stained with Sytox Green and observed by fluorescence microscopy. Human pulmonary microvascular endothelial cells were stimulated with NETs, and the experimental group was pretreated with colchicine (7.5, 15nmol/L), and the markers of inflammation and pyroptosis were detected 24h later. Results: (1) Pathological staining of lung tissue showed that colchicine treatment significantly alleviated interstitial lung disease in EAM mice. (2) After colchicine treatment, the infiltration of NETs in the lung tissue of EAM was significantly reduced, and the serum level of NETs was also significantly decreased (F=6.859, P < 0.05). (3) Colchicine intervention significantly attenuated the formation of NETs on neutrophils induced by PMA in vitro. (4) Colchicine significantly decreased the expression of inflammasomes and pyroptosis markers in NETs-stimulated human lung microvascular endothelial cells, and inhibited the production of inflammasomes and pyroptosis in the lung tissue of EAM in vivo. Conclusions: Colchicine can alleviate interstitial lung disease in EAM mice by inhibiting NETs formation, inflammasome activation and endothelial cell pyroptosis. These findings provide a basis for targeting NETs in the treatment of myositis-associated interstitial lung disease. | ||
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| 700 | 1 | |a Zhao, Peipei |4 aut | |
| 700 | 1 | |a Zhao, Liangtao |4 aut | |
| 700 | 1 | |a Bai, Ling |4 aut | |
| 700 | 1 | |a Su, Qiyan |4 aut | |
| 700 | 1 | |a Feng, Yingyue |4 aut | |
| 700 | 1 | |a Ma, Wenlan |4 aut | |
| 700 | 1 | |a Zhu, Jiarui |4 aut | |
| 700 | 1 | |a Zhang, Sigong |4 aut | |
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