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Direct effects of m...
Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses
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- Ramu, Sangeetha (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Akbarshahi, Hamid (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Translationell lungmedicin,Respiratory Immunopharmacology,Lund University Research Groups,Translational Respiratory Medicine
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- Mogren, Sofia (author)
- Lund University,Lunds universitet,Respiratorisk cellbiologi,Forskargrupper vid Lunds universitet,Respiratory Cell Biology,Lund University Research Groups
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- Berlin, Frida (author)
- Lund University,Lunds universitet,Respiratorisk cellbiologi,Forskargrupper vid Lunds universitet,Respiratory Cell Biology,Lund University Research Groups
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- Cerps, Samuel (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Menzel, Mandy (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Hvidtfeldt, Morten (author)
- Frederiksberg Hospital
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- Porsbjerg, Celeste (author)
- Frederiksberg Hospital
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- Uller, Lena (author)
- Lund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups
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- Andersson, Cecilia K. (author)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Respiratorisk immunofarmakologi,Respiratorisk cellbiologi,Airway Inflammation and Immunology,Lund University Research Groups,Respiratory Immunopharmacology,Respiratory Cell Biology
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(creator_code:org_t)
- 2021-06-02
- 2021
- English.
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In: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 22:1
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Asthma
- Chymase
- Human bronchial epithelial cells
- Mast cells
- Tryptase
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Ramu, Sangeetha
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Akbarshahi, Hami ...
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Mogren, Sofia
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Berlin, Frida
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Cerps, Samuel
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Menzel, Mandy
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Hvidtfeldt, Mort ...
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Porsbjerg, Celes ...
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Uller, Lena
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Andersson, Cecil ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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BMC Immunology
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Lund University