Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses

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Ramu, SangeethaLund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups (author)

Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses

Article/chapterEnglish2021

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2021-06-02
Springer Science and Business Media LLC,2021

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LIBRIS-ID:oai:lup.lub.lu.se:b72ea12c-7634-4504-a0df-1193619f41ef
https://lup.lub.lu.se/record/b72ea12c-7634-4504-a0df-1193619f41efURI
https://doi.org/10.1186/s12865-021-00424-wDOI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

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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 and genre

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
Asthma
Chymase
Human bronchial epithelial cells
Mast cells
Tryptase

Added entries (persons, corporate bodies, meetings, titles ...)

Akbarshahi, HamidLund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Translationell lungmedicin,Respiratory Immunopharmacology,Lund University Research Groups,Translational Respiratory Medicine(Swepub:lu)med-hab (author)
Mogren, SofiaLund University,Lunds universitet,Respiratorisk cellbiologi,Forskargrupper vid Lunds universitet,Respiratory Cell Biology,Lund University Research Groups(Swepub:lu)so0187mo (author)
Berlin, FridaLund University,Lunds universitet,Respiratorisk cellbiologi,Forskargrupper vid Lunds universitet,Respiratory Cell Biology,Lund University Research Groups(Swepub:lu)fr4827be (author)
Cerps, SamuelLund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups(Swepub:lu)sa7111ce (author)
Menzel, MandyLund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups(Swepub:lu)med-mym (author)
Hvidtfeldt, MortenFrederiksberg Hospital (author)
Porsbjerg, CelesteFrederiksberg Hospital (author)
Uller, LenaLund University,Lunds universitet,Respiratorisk immunofarmakologi,Forskargrupper vid Lunds universitet,Respiratory Immunopharmacology,Lund University Research Groups(Swepub:lu)mphy-lul (author)
Andersson, Cecilia K.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(Swepub:lu)ce4613an (author)
Respiratorisk immunofarmakologiForskargrupper vid Lunds universitet (creator_code:org_t)

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In:BMC Immunology: Springer Science and Business Media LLC22:11471-2172

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