Adenosine metabolism inhibits airway inflammation and remodeling in asthma model induced by Aspergillus fumigatus
Abstract Background: Given that severe inflammatory reaction is an important manifestation of asthma, it would be helpful to understand the pathological mechanism of asthma to determine the endogenous anti-inflammatory events of asthma. Recent studies have found that energy metabolites in the body are related to some inflammatory diseases, but little is known about their role in asthma. Method: In this study, an asthma model was established by intratracheal instillation of Aspergillus fumigatus extract in Ecto-5'-Nucleotidase (CD73) gene–knockout and wild-type mice. Multiple analyses from bronchoalveolar lavage fluid (BALF) were used to determine the levels of cytokines and chemokines. Immunohistochemistry was used to detect subcutaneous fibrosis and inflammatory cell infiltration. Finally, adenosine 5’-(α, β-methylene) diphosphate (APCP), a CD73 inhibitor, was pumped subcutaneously before Aspergillus attack to observe the infiltration of inflammatory cells and subcutaneous fibrosis to clarify its therapeutic effect. Result: PAS staining showed that CD73 knockout inhibited pulmonary epithelial cell proliferation and bronchial fibrosis induced by Aspergillus extract. The genetic destruction of CD73 significantly reduced the production of Th2 cytokines, interleukin (IL)-4, IL-6, IL-13, chemokine (C-C motif) ligand 5 (CCL5), eosinophil chemokine, neutrophil IL-17, and granulocyte colony-stimulating factor (G-CSF). In addition, exogenous adenosine supplementation increased airway inflammation. Finally, the CD73 inhibitor APCP was administered to reduce inflammation and subcutaneous fibrosis. Conclusion: Elevated adenosine metabolism plays an inflammatory role in asthma, and CD73 could be a potential therapeutic target for asthma..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
ResearchSquare.com - (2023) vom: 18. Aug. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
liu, tingting [VerfasserIn] |
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| doi: |
10.21203/rs.3.rs-2448772/v1 |
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| PPN (Katalog-ID): |
XRA038423162 |
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| 245 | 1 | 0 | |a Adenosine metabolism inhibits airway inflammation and remodeling in asthma model induced by Aspergillus fumigatus |
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| 520 | |a Abstract Background: Given that severe inflammatory reaction is an important manifestation of asthma, it would be helpful to understand the pathological mechanism of asthma to determine the endogenous anti-inflammatory events of asthma. Recent studies have found that energy metabolites in the body are related to some inflammatory diseases, but little is known about their role in asthma. Method: In this study, an asthma model was established by intratracheal instillation of Aspergillus fumigatus extract in Ecto-5'-Nucleotidase (CD73) gene–knockout and wild-type mice. Multiple analyses from bronchoalveolar lavage fluid (BALF) were used to determine the levels of cytokines and chemokines. Immunohistochemistry was used to detect subcutaneous fibrosis and inflammatory cell infiltration. Finally, adenosine 5’-(α, β-methylene) diphosphate (APCP), a CD73 inhibitor, was pumped subcutaneously before Aspergillus attack to observe the infiltration of inflammatory cells and subcutaneous fibrosis to clarify its therapeutic effect. Result: PAS staining showed that CD73 knockout inhibited pulmonary epithelial cell proliferation and bronchial fibrosis induced by Aspergillus extract. The genetic destruction of CD73 significantly reduced the production of Th2 cytokines, interleukin (IL)-4, IL-6, IL-13, chemokine (C-C motif) ligand 5 (CCL5), eosinophil chemokine, neutrophil IL-17, and granulocyte colony-stimulating factor (G-CSF). In addition, exogenous adenosine supplementation increased airway inflammation. Finally, the CD73 inhibitor APCP was administered to reduce inflammation and subcutaneous fibrosis. Conclusion: Elevated adenosine metabolism plays an inflammatory role in asthma, and CD73 could be a potential therapeutic target for asthma. | ||
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| 700 | 1 | |a Wang, Yue-li |4 aut | |
| 700 | 1 | |a Zhang, Zhi |4 aut | |
| 700 | 1 | |a Jia, Li-xin |4 aut | |
| 700 | 1 | |a Zhang, Jing |4 aut | |
| 700 | 1 | |a Chen, Zhi-hua |4 aut | |
| 700 | 1 | |a Shen, Hua-hao |4 aut | |
| 700 | 1 | |a Piao, Chun-mei |4 aut | |
| 700 | 1 | |a Du, Jie |4 aut | |
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