Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses
Abstract Background Mast cells (MCs) are known to contribute to both acute and chronic inflammation. Bronchial epithelial cells are the first line of defence against pathogens and a deficient anti-viral response has been suggested to play a role in the pathogenesis of asthma exacerbations. However,...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | BMC Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12865-021-00424-w |
| _version_ | 1818437455776317440 |
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| author | Sangeetha Ramu Hamid Akbarshahi Sofia Mogren Frida Berlin Samuel Cerps Mandy Menzel Morten Hvidtfeldt Celeste Porsbjerg Lena Uller Cecilia K. Andersson |
| author_facet | Sangeetha Ramu Hamid Akbarshahi Sofia Mogren Frida Berlin Samuel Cerps Mandy Menzel Morten Hvidtfeldt Celeste Porsbjerg Lena Uller Cecilia K. Andersson |
| author_sort | Sangeetha Ramu |
| collection | DOAJ |
| description | Abstract Background Mast cells (MCs) are known to contribute to both acute and chronic inflammation. Bronchial epithelial cells are the first line of defence against pathogens and a deficient anti-viral response has been suggested to play a role in the pathogenesis of asthma exacerbations. However, effects of MC mediators on bronchial epithelial immune response have been less studied. The aim of this study is to investigate the direct effects of stimulation with MC proteases, tryptase and chymase, on inflammatory and anti-viral responses in human bronchial epithelial cells (HBECs). Method Cultured BEAS-2b cells and primary HBECs from 3 asthmatic patients were stimulated with tryptase or chymase (0.1 to 0.5 μg/ml) for 1, 3, 6 and 24 h. To study the effects of MC mediators on the anti-viral response, cells were stimulated with 10 μg/ml of viral mimic Poly (I:C) for 3 and 24 h following pre-treatment with 0.5 μg/ml tryptase or chymase for 3 h. Samples were analysed for changes in pro-inflammatory and anti-viral mediators and receptors using RT-qPCR, western blot and Luminex. Results Tryptase and chymase induced release of the alarmin ATP and pro-inflammatory mediators IL-8, IL-6, IL-22 and MCP-1 from HBECs. Moreover, tryptase and chymase decreased the expression of E-cadherin and zonula occludens-1 expression from HBECs. Pre-treatment of HBECs with tryptase and chymase further increased Poly (I:C) induced IL-8 release at 3 h. Furthermore, tryptase significantly reduced type-I and III interferons (IFNs) and pattern recognition receptor (PRR) expression in HBECs. Tryptase impaired Poly (I:C) induced IFN and PRR expression which was restored by treatment of a serine protease inhibitor. Similar effects of tryptase on inflammation and anti-viral responses were also confirmed in primary HBECs from asthmatic patients. Conclusion MC localization within the epithelium and the release of their proteases may play a critical role in asthma pathology by provoking pro-inflammatory and alarmin responses and downregulating IFNs. Furthermore, MC proteases induce downregulation of epithelial junction proteins which may lead to barrier dysfunction. In summary, our data suggests that mast cells may contribute towards impaired anti-viral epithelial responses during asthma exacerbations mediated by the protease activity of tryptase. |
| first_indexed | 2024-12-14T17:24:57Z |
| format | Article |
| id | doaj.art-abc116dee2964053bb80f7192e788dae |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-12-14T17:24:57Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-abc116dee2964053bb80f7192e788dae2022-12-21T22:53:14ZengBMCBMC Immunology1471-21722021-06-0122111210.1186/s12865-021-00424-wDirect effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responsesSangeetha Ramu0Hamid Akbarshahi1Sofia Mogren2Frida Berlin3Samuel Cerps4Mandy Menzel5Morten Hvidtfeldt6Celeste Porsbjerg7Lena Uller8Cecilia K. Andersson9Department of Experimental Medical Science, Lund UniversityDepartment of Experimental Medical Science, Lund UniversityDepartment of Experimental Medical Science, Lund UniversityDepartment of Experimental Medical Science, Lund UniversityDepartment of Experimental Medical Science, Lund UniversityDepartment of Experimental Medical Science, Lund UniversityDepartment of Respiratory Medicine, Bispebjerg and Frederiksberg HospitalDepartment of Respiratory Medicine, Bispebjerg and Frederiksberg HospitalDepartment of Experimental Medical Science, Lund UniversityDepartment of Experimental Medical Science, Lund UniversityAbstract Background Mast cells (MCs) are known to contribute to both acute and chronic inflammation. Bronchial epithelial cells are the first line of defence against pathogens and a deficient anti-viral response has been suggested to play a role in the pathogenesis of asthma exacerbations. However, effects of MC mediators on bronchial epithelial immune response have been less studied. The aim of this study is to investigate the direct effects of stimulation with MC proteases, tryptase and chymase, on inflammatory and anti-viral responses in human bronchial epithelial cells (HBECs). Method Cultured BEAS-2b cells and primary HBECs from 3 asthmatic patients were stimulated with tryptase or chymase (0.1 to 0.5 μg/ml) for 1, 3, 6 and 24 h. To study the effects of MC mediators on the anti-viral response, cells were stimulated with 10 μg/ml of viral mimic Poly (I:C) for 3 and 24 h following pre-treatment with 0.5 μg/ml tryptase or chymase for 3 h. Samples were analysed for changes in pro-inflammatory and anti-viral mediators and receptors using RT-qPCR, western blot and Luminex. Results Tryptase and chymase induced release of the alarmin ATP and pro-inflammatory mediators IL-8, IL-6, IL-22 and MCP-1 from HBECs. Moreover, tryptase and chymase decreased the expression of E-cadherin and zonula occludens-1 expression from HBECs. Pre-treatment of HBECs with tryptase and chymase further increased Poly (I:C) induced IL-8 release at 3 h. Furthermore, tryptase significantly reduced type-I and III interferons (IFNs) and pattern recognition receptor (PRR) expression in HBECs. Tryptase impaired Poly (I:C) induced IFN and PRR expression which was restored by treatment of a serine protease inhibitor. Similar effects of tryptase on inflammation and anti-viral responses were also confirmed in primary HBECs from asthmatic patients. Conclusion MC localization within the epithelium and the release of their proteases may play a critical role in asthma pathology by provoking pro-inflammatory and alarmin responses and downregulating IFNs. Furthermore, MC proteases induce downregulation of epithelial junction proteins which may lead to barrier dysfunction. In summary, our data suggests that mast cells may contribute towards impaired anti-viral epithelial responses during asthma exacerbations mediated by the protease activity of tryptase.https://doi.org/10.1186/s12865-021-00424-wAsthmaMast cellsTryptaseChymaseHuman bronchial epithelial cells |
| spellingShingle | Sangeetha Ramu Hamid Akbarshahi Sofia Mogren Frida Berlin Samuel Cerps Mandy Menzel Morten Hvidtfeldt Celeste Porsbjerg Lena Uller Cecilia K. Andersson Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses BMC Immunology Asthma Mast cells Tryptase Chymase Human bronchial epithelial cells |
| title | Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses |
| title_full | Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses |
| title_fullStr | Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses |
| title_full_unstemmed | Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses |
| title_short | Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses |
| title_sort | direct effects of mast cell proteases tryptase and chymase on bronchial epithelial integrity proteins and anti viral responses |
| topic | Asthma Mast cells Tryptase Chymase Human bronchial epithelial cells |
| url | https://doi.org/10.1186/s12865-021-00424-w |
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