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The non-proteolytic house dust mite allergen Der p 2 induce NF-kappaB and MAPK dependent activation of bronchial epithelial cells.
Clin Exp Allergy. 2009 Aug; 39(8):1199-208.CE

Abstract

BACKGROUND

House dust mites (HDM) are well-known as a source of indoor aeroallergens and for causing allergic airway diseases. Some proteolytic HDM allergens are known to activate respiratory epithelial cells to produce pro-inflammatory mediators, while there is limited knowledge regarding such activity among non-proteolytic HDM allergens.

OBJECTIVE

To investigate whether Der p 2, a major non-proteolytic allergen of Dermatophagoides pteronyssinus, activates respiratory epithelial cells to produce mediators involved in asthma pathogenesis and to elucidate the mechanism of such activation.

METHODS

The human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial (NHBE) cells and the alveolar epithelial cell line A549 were exposed to recombinant Der p 2. Following exposure, we analysed a panel of soluble mediators and cell adhesion receptors involved in asthma pathogenesis by promoting recruitment, survival and binding of inflammatory cells. The involvement of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was studied using specific inhibitors.

RESULTS

Der p 2 activated bronchial BEAS-2B and NHBE cells, but not alveolar A549 cells. In BEAS-2B cells Der p 2 induced dose-dependent up-regulation in both mRNA level and protein secretion of granulocyte-macrophage colony-stimulating factor, IL-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3alpha. Secretion as well as surface expression of intercellular adhesion molecule (ICAM)-1 was also up-regulated, which was associated with increased adhesion of monocytes to the epithelial cells. The release of cytokines and chemokines was regulated by NF-kappaB and MAPK activation in different ways, while expression of ICAM-1 was solely dependent on NF-kappaB activation.

CONCLUSION

These results show that Der p 2 activates respiratory epithelial cells, indicating that this non-proteolytic allergen, in addition to its immunogenic properties, can aggravate respiratory airway disease by adjuvant-like activation of the lung epithelium.

Authors+Show Affiliations

Swedish Defence Research Agency, FOI CBRN Defence and Security, Umeå, Sweden. camilla.osterlund@foi.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19486032

Citation

Osterlund, C, et al. "The Non-proteolytic House Dust Mite Allergen Der P 2 Induce NF-kappaB and MAPK Dependent Activation of Bronchial Epithelial Cells." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 39, no. 8, 2009, pp. 1199-208.
Osterlund C, Grönlund H, Polovic N, et al. The non-proteolytic house dust mite allergen Der p 2 induce NF-kappaB and MAPK dependent activation of bronchial epithelial cells. Clin Exp Allergy. 2009;39(8):1199-208.
Osterlund, C., Grönlund, H., Polovic, N., Sundström, S., Gafvelin, G., & Bucht, A. (2009). The non-proteolytic house dust mite allergen Der p 2 induce NF-kappaB and MAPK dependent activation of bronchial epithelial cells. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 39(8), 1199-208. https://doi.org/10.1111/j.1365-2222.2009.03284.x
Osterlund C, et al. The Non-proteolytic House Dust Mite Allergen Der P 2 Induce NF-kappaB and MAPK Dependent Activation of Bronchial Epithelial Cells. Clin Exp Allergy. 2009;39(8):1199-208. PubMed PMID: 19486032.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The non-proteolytic house dust mite allergen Der p 2 induce NF-kappaB and MAPK dependent activation of bronchial epithelial cells. AU - Osterlund,C, AU - Grönlund,H, AU - Polovic,N, AU - Sundström,S, AU - Gafvelin,G, AU - Bucht,A, Y1 - 2009/05/26/ PY - 2009/6/3/entrez PY - 2009/6/3/pubmed PY - 2009/12/18/medline SP - 1199 EP - 208 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin. Exp. Allergy VL - 39 IS - 8 N2 - BACKGROUND: House dust mites (HDM) are well-known as a source of indoor aeroallergens and for causing allergic airway diseases. Some proteolytic HDM allergens are known to activate respiratory epithelial cells to produce pro-inflammatory mediators, while there is limited knowledge regarding such activity among non-proteolytic HDM allergens. OBJECTIVE: To investigate whether Der p 2, a major non-proteolytic allergen of Dermatophagoides pteronyssinus, activates respiratory epithelial cells to produce mediators involved in asthma pathogenesis and to elucidate the mechanism of such activation. METHODS: The human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial (NHBE) cells and the alveolar epithelial cell line A549 were exposed to recombinant Der p 2. Following exposure, we analysed a panel of soluble mediators and cell adhesion receptors involved in asthma pathogenesis by promoting recruitment, survival and binding of inflammatory cells. The involvement of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was studied using specific inhibitors. RESULTS: Der p 2 activated bronchial BEAS-2B and NHBE cells, but not alveolar A549 cells. In BEAS-2B cells Der p 2 induced dose-dependent up-regulation in both mRNA level and protein secretion of granulocyte-macrophage colony-stimulating factor, IL-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3alpha. Secretion as well as surface expression of intercellular adhesion molecule (ICAM)-1 was also up-regulated, which was associated with increased adhesion of monocytes to the epithelial cells. The release of cytokines and chemokines was regulated by NF-kappaB and MAPK activation in different ways, while expression of ICAM-1 was solely dependent on NF-kappaB activation. CONCLUSION: These results show that Der p 2 activates respiratory epithelial cells, indicating that this non-proteolytic allergen, in addition to its immunogenic properties, can aggravate respiratory airway disease by adjuvant-like activation of the lung epithelium. SN - 1365-2222 UR - https://www.unboundmedicine.com/medline/citation/19486032/The_non_proteolytic_house_dust_mite_allergen_Der_p_2_induce_NF_kappaB_and_MAPK_dependent_activation_of_bronchial_epithelial_cells_ L2 - https://doi.org/10.1111/j.1365-2222.2009.03284.x DB - PRIME DP - Unbound Medicine ER -