Correlation between CCL26 production by human bronchial epithelial cells and airway eosinophils: Involvement in patients with severe eosinophilic asthma - 06/10/15
Abstract |
Background |
High pulmonary eosinophil counts are associated with asthma symptoms and severity. Bronchial epithelial cells (BECs) produce CC chemokines, notably CCL26 (eotaxin-3), which recruits and activates eosinophils from asthmatic patients. This suggests that CCL26 production by BECs might be involved in persistent eosinophilia in patients with severe asthma despite treatment with high corticosteroid doses.
Objective |
We sought to determine whether CCL26 levels correlate with eosinophilia and asthma severity.
Methods |
Human CC chemokine expression was assessed by means of quantitative PCR or a quantitative PCR array in vehicle- or IL-13–treated BECs. CCL26 was quantitated by means of ELISA. Immunohistochemistry analyses of CCL26 and major basic protein were done on bronchial biopsy specimens.
Results |
IL-13 selectively induced CCL26 expression by BECs. This increase was time-dependent and more prominent in BECs from patients with severe eosinophilic asthma. CCL26 levels measured in supernatants of IL-13–stimulated BECs also increased with asthma severity as follows: patients with severe eosinophilic asthma > patients with mild asthma ≈ healthy subjects. Immunohistochemistry analyses of bronchial biopsy specimens confirmed increased levels of CCL26 in the epithelium of patients with mild and those with severe eosinophilic asthma. Tissue eosinophil counts did not correlate with CCL26 staining. However, sputum CCL26 levels significantly correlated with sputum eosinophil counts (P < .0001), suggesting that CCL26 participates in the movement of eosinophils from the tissues to the airway lumen.
Conclusions |
These results show a relation between CCL26 production by IL-13–stimulated BECs, sputum eosinophil counts, and asthma severity. They also suggest a role for CCL26 in the sustained inflammation observed in patients with severe eosinophilic asthma and reveal CCL26 as a potential target for treating patients with eosinophilic asthma that are refractory to classic therapies.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, bronchial epithelial cells, chemokine, eotaxin, CCL26, IL-13, bronchial mucosa, inflammation, severe asthma
Abbreviations used : BEC, JAK, MBP, qPCR, SOCS, STAT6
Plan
| Supported by a grant to M.L. and N.F. from the Fondation de l’IUCPQ and the J-D-Bégin Research Chair. M.-C.L. was supported by scholarships from La fondation Wilbrod-Bhérer et Joseph-Demers de l’Université Laval, la direction de la recherche universitaire de l’IUCPQ and the CIHR–Quebec Respiratory Health Training Program. N.F. was supported by a salary award from the Fonds de la recherche du Québec-Santé. |
|
| Disclosure of potential conflict of interest: M.-C. Larose has received scholarships from the Canadian Institutes of Health Research–Quebec Respiratory Health Training Program, Fondation Wilbrod-Bhérer et Joseph-Demers de l'Université Laval, and La direction de la recherche universitaire de l'IUCPQ. M. Laviolette has received payment for lectures from Boston Scientific. N. Flamand has received research support from Fondation de l'IUCPQ and the Canadian Institutes of Health Research (MOP-97930). The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 136 - N° 4
P. 904-913 - octobre 2015 Retour au numéro
Article précédent
- Polymorphisms related to ORMDL3 are associated with asthma susceptibility, alterations in transcriptional regulation of ORMDL3, and changes in TH2 cytokine levels
- Michaela Schedel, Sven Michel, Vincent D. Gaertner, Antoaneta A. Toncheva, Martin Depner, Aristea Binia, Maximilian Schieck, Marie T. Rieger, Norman Klopp, Andrea von Berg, Albrecht Bufe, Otto Laub, Ernst Rietschel, Andrea Heinzmann, Burkard Simma, Christian Vogelberg, Jon Genuneit, Thomas Illig, Michael Kabesch
- Magnitude of effect of asthma treatments on Asthma Quality of Life Questionnaire and Asthma Control Questionnaire scores: Systematic review and network meta-analysis
- Eric D. Bateman, Dirk Esser, Costel Chirila, Maria Fernandez, Andy Fowler, Petra Moroni-Zentgraf, J. Mark FitzGerald
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?