Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers - 18/04/17
Abstract |
Background |
Air pollution's association with asthma may be due to its augmentation of allergenic effects, but the role of microRNA (miRNA) and gene expression in this synergy is unknown.
Objective |
We sought to determine whether exposure to allergen, exposure to diesel exhaust (DE), or coexposures modulate miRNA, gene expression, or inflammatory pathways and whether these measurements are correlated.
Methods |
Fifteen participants with atopy completed this controlled study of 2 hours of filtered air or DE (300 μg PM2.5/m3) exposure, followed by saline-controlled segmental bronchial allergen challenge. Gene and miRNA expression in bronchial brushings and lung inflammatory markers were measured 48 hours later, in study arms separated by approximately 4 weeks. Expression of miRNAs, messenger RNAs, and inflammatory markers and their interrelationships were determined using regression.
Results |
Robust linear models indicated that DE plus saline and DE plus allergen significantly modulated the highest number of miRNAs and messenger RNAs, respectively, relative to control (filtered air plus saline). In mixed models, allergen exposure modulated (q ≤ 0.2) miRNAs including miR-183-5p, miR-324-5p, and miR-132-3p and genes including NFKBIZ and CDKN1A, but DE did not significantly modify this allergenic effect. Repression of CDKN1A by allergen-induced miR-132-3p may contribute to shedding of bronchial epithelial cells.
Conclusions |
Expression of specific miRNAs and genes associated with bronchial immune responses were significantly modulated by DE or allergen. However, DE did not augment the effect of allergen at 48 hours, suggesting that adjuvancy may be transient or require higher or prolonged exposure. In silico analysis suggested a possible mechanism contributing to epithelial wall damage following allergen exposure.
El texto completo de este artículo está disponible en PDF.Key words : Air pollution, allergy, controlled human exposure, inflammatory markers, multi-omics
Abbreviations used : BAL, BEC, DE, DEA, DES, FAA, FAS, GO, miRNA, mRNA, PLS, PM
Esquema
| This research was supported by funding from AllerGen NCE Inc (Allergy, Genes and Environment Network, GxE2; GxE4), WorkSafeBC (RG2011-OG07), the BC Lung Association, and the Canadian Institutes of Health Research (CIHR, MOP 123319). C.F.R. was supported by a Vancouver Coastal Health Research Institute - Centre for Respiratory, Cardiac and Critical Care Medicine Fellowship. M.Y. was supported by fellowships from the CIHR Integrated and Mentored Pulmonary and Cardiovascular Training Program (IMPACT), the Sumitomo Life Social Welfare Services Foundation, and the Mochida Memorial Foundation for Medical and Pharmaceutical Research. A.S. was the recipient of the CIHR Doctoral Award Frederick Banting and Charles Best Canada Graduate Scholarship. |
|
| Disclosure of potential conflict of interest: C. F. Rider has received funding from the Vancouver Coastal Health Research Institute, AstraZeneca, and GlaxoSmithKline and has received travel support from AllerGen NCE Inc. M. Yamamoto has received a grant and travel support from Canadian Institutes for Health Research-IMPACT. O. P. Günther has received a consulting fee/honorarium from the University of British Columbia Department of Medicine. J. A. Hirota has consultant arrangements with Qu Biologics. C. Carlsten has received grants from AllerGen NCE Inc (Allergy, Genes, and Environment Network), WorkSafe BC, the British Columbia Lung Association, and the Canadian Institutes of Health Research. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 138 - N° 6
P. 1690-1700 - décembre 2016 Regresar al número
Artículo precedente
- X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene
- Chantal Lagresle-Peyrou, Sonia Luce, Farid Ouchani, Tayebeh Shabi Soheili, Hanem Sadek, Myriam Chouteau, Amandine Durand, Isabelle Pic, Jacek Majewski, Chantal Brouzes, Nathalie Lambert, Armelle Bohineust, Els Verhoeyen, François-Loïc Cosset, Aude Magerus-Chatinet, Frédéric Rieux-Laucat, Virginie Gandemer, Delphine Monnier, Catherine Heijmans, Marielle van Gijn, Virgil A. Dalm, Nizar Mahlaoui, Jean-Louis Stephan, Capucine Picard, Anne Durandy, Sven Kracker, Claire Hivroz, Nada Jabado, Geneviève de Saint Basile, Alain Fischer, Marina Cavazzana, Isabelle André-Schmutz
- The association of asthma, total IgE, and blood lead and cadmium levels
- Sangshin Park, Eun-Hee Lee, Younglim Kho
Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
El acceso al texto completo de este artículo requiere una suscripción.
¿Ya suscrito a @@106933@@ revista ?