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Non-proteolytic aeroallergens from mites, cat and dog exert adjuvant-like activation of bronchial epithelial cells
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
2011 (English)In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 155, no 2, 111-118 p.Article in journal (Refereed) Published
Abstract [en]

Background: Exposure to seasonal or indoor allergens may cause sensitisation and development of allergic airway diseases. We have previously demonstrated that the non-proteolytic major house dust mite (HDM) allergen Der p 2 stimulates pro-inflammatory responses in bronchial epithelial cells. We aimed to determine if other clinically relevant non-proteolytic aeroallergens originating from HDMs, storage mites, cat, dog, birch and timothy also activate respiratory epithelial cells.

Methods: Cultures of human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial cells and alveolar epithelial cell line A549 were exposed to recombinant (r)Der p 2, natural (n)Der f 2, rEur m 2, rLep d 2, rFel d 1, nFel d 1, rCan f 2, rBet v 1 or rPhl p 5a. A panel of secreted mediators and expression of cell adhesion receptors involved in recruitment, survival and adhesion of inflammatory cells in asthmatic airways was assessed.

Results: The mite allergens rDer p 2, nDer f 2, rEur m 2 and rLep d 2 as well as the cat and dog allergens rFel d 1, nFel d 1 and rCan f 2 induced granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3α secretion from bronchial epithelial cells as well as surface expression of intracellular adhesion molecule-1. The pollen allergens rBet v 1 and rPhl p 5a from birch and timothy did not activate the cells. None of the studied allergens affected the alveolar epithelial cells.

Conclusion: These results show that both mite and structurally unrelated cat and dog allergens can activate respiratory epithelial cells by adjuvant-like protease-independent mechanisms.

Place, publisher, year, edition, pages
2011. Vol. 155, no 2, 111-118 p.
Keyword [en]
house-dust mite; factor-kappa-b; allergen fel-d-1; inflammatory response; lipocalin proteins; major allergen; amino-acid; asthma; lung; expression
National Category
Respiratory Medicine and Allergy Immunology in the medical area
URN: urn:nbn:se:umu:diva-39542DOI: 10.1159/000318743PubMedID: 21196755OAI: diva2:393598
Available from: 2011-01-31 Created: 2011-01-31 Last updated: 2012-02-02Bibliographically approved
In thesis
1. Activation of lung epithelial cells by group 2 mite allergens
Open this publication in new window or tab >>Activation of lung epithelial cells by group 2 mite allergens
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Throughout many parts of the world house dust mites (HDM) are considered as a major source of indoor aeroallergens and they are powerful inducers of allergic diseases. Proteolytic HDM allergens are recognised as being able to directly activate respiratory epithelial cells and thereby actively participate in innate immune responses. Although several major HDM allergens lack proteolytic activity, their possible ability to similarly interact with epithelial cells is not known.

The overall aim of this thesis was therefore to elucidate if and how major non-proteolytic group 2 allergens from different mite species interact with respiratory epithelial cells. The effects of the structurally related Der p 2, Der f 2 and Eur m 2 from different HDM species as well as the storage mite allergen Lep d 2 were studied in vitro using human respiratory epithelial cells. Also the non-proteolytic, but structurally dissimilar, Fel d 1 from cat, Can f 2 from dog, Bet v 1 from birch and Phl p 5a from timothy were studied.

In this thesis evidence that major group 2 mite allergens activate bronchial epithelial cells is presented. Following allergen exposure the secreted amount of the inflammatory mediators G-CSF, GM-CSF, IL-6, IL-8, MCP-1, MIP-3α and sICAM-1 was increased. Surface expression of ICAM-1 was also increased following allergen exposure. Moreover, Fel d 1 and Can f 2 induced secretion of the same mediators from bronchial epithelial cells, representing two additional protein structures being able to directly induce cell activation. In experiments using specific inhibitors and siRNA transfection, it was shown that the mite allergens engage TLR4 and activation through MyD88, MAPK and NF-κB signal transduction pathways.

In conclusion, the novel findings in this thesis provide knowledge on how major aeroallergens, in addition to their ability to provoke specific adaptive immune responses, may aggravate a respiratory airway disease by adjuvant-like activation of inflammatory responses in bronchial epithelial cells. This differs from previously reported allergen-induction of epithelial cells by the clear independency of proteolytic activation.

Place, publisher, year, edition, pages
Umeå universitet, 2012. 59 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1467
group 2 mite allergens, Der p 2, Der f 2, Eur m 2, Lep d 2, airway epithelium
National Category
Cell and Molecular Biology
Research subject
Lung Medicine
urn:nbn:se:umu:diva-51619 (URN)978-91-7459-339-6 (ISBN)
Public defence
2012-02-23, E04, Byggnad 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Available from: 2012-02-02 Created: 2012-01-30 Last updated: 2012-02-02Bibliographically approved

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