Age dictates a steroid-resistant cascade of Wnt5a, transglutaminase 2, and leukotrienes in inflamed airways.

Détails

ID Serval
serval:BIB_28A192AC4E7B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Age dictates a steroid-resistant cascade of Wnt5a, transglutaminase 2, and leukotrienes in inflamed airways.
Périodique
The Journal of allergy and clinical immunology
Auteur⸱e⸱s
Dietz K., de Los Reyes Jiménez M., Gollwitzer E.S., Chaker A.M., Zissler U.M., Rådmark O.P., Baarsma H.A., Königshoff M., Schmidt-Weber C.B., Marsland B.J., Esser-von Bieren J.
ISSN
1097-6825 (Electronic)
ISSN-L
0091-6749
Statut éditorial
Publié
Date de publication
04/2017
Peer-reviewed
Oui
Volume
139
Numéro
4
Pages
1343-1354.e6
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Airway remodeling is a detrimental and refractory process showing age-dependent clinical manifestations that are mechanistically undefined. The leukotriene (LT) and wingless/integrase (Wnt) pathways have been implicated in remodeling, but age-specific expression profiles and common regulators remained elusive.
We sought to study the activation of the LT and Wnt pathways during early- or late-onset allergic airway inflammation and to address regulatory mechanisms and clinical relevance in normal human bronchial epithelial cells (NHBEs) and nasal polyp tissues.
Mice were sensitized with house dust mite (HDM) allergens from days 3, 15, or 60 after birth. Remodeling factors in murine bronchoalveolar lavage fluid, lung tissue, or human nasal polyp tissue were analyzed by means of Western blotting, immunoassays, or histology. Regulatory mechanisms were studied in cytokine/HDM-stimulated NHBEs and macrophages.
Bronchoalveolar lavage fluid LT levels were increased in neonatal and adult but reduced in juvenile HDM-sensitized mice. Lungs of neonatally sensitized mice showed increased 5-lipoxygenase levels, whereas adult mice expressed more group 10 secretory phospholipase A2, Wnt5a, and transglutaminase 2 (Tgm2). Older mice showed colocalization of Wnt5a and LT enzymes in the epithelium, a pattern also observed in human nasal polyps. IL-4 promoted epithelial Wnt5a secretion, which upregulated macrophage Tgm2 expression, and Tgm2 inhibition in turn reduced LT release. Tgm2, group 10 secretory phospholipase A2, and LT enzymes in NHBEs and nasal polyps were refractory to corticosteroids.
Our findings reveal age differences in LT and Wnt pathways during airway inflammation and identify a steroid-resistant cascade of Wnt5a, Tgm2, and LTs, which might represent a therapeutic target for airway inflammation and remodeling.

Mots-clé
Aging/immunology, Airway Remodeling/immunology, Animals, Asthma/immunology, Blotting, Western, Bronchial Hyperreactivity/immunology, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, GTP-Binding Proteins/immunology, Humans, Leukotrienes/immunology, Mice, Nasal Polyps/immunology, Pneumonia/immunology, Transglutaminases/immunology, Wnt-5a Protein/immunology, Age, Wnt5a, airway inflammation, airway remodeling, allergy, asthma, bronchial epithelial cells, house dust mite, leukotrienes, lipid mediators, nasal polyps, secretory phospholipase A(2), transglutaminase 2
Pubmed
Web of science
Création de la notice
16/09/2016 9:51
Dernière modification de la notice
20/08/2019 13:08
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