Activation of lung epithelial cells by group 2 mite allergens
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
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
Cell and Molecular Biology
Research subject Lung Medicine
IdentifiersURN: urn:nbn:se:umu:diva-51619ISBN: 978-91-7459-339-6OAI: oai:DiVA.org:umu-51619DiVA: diva2:485790
2012-02-23, E04, Byggnad 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Bucht, AndersSandström, Thomas
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