Increased T-cell survival by structural bronchial cells derived from asthmatic subjects cultured in an engineered human mucosa - 15/08/11
Reprint requests: Jamila Chakir, PhD, Centre de recherche, Hôpital Laval, 2725 Chemin Sainte-Foy, Sainte-Foy, Québec, Canada, G1V 4G5.Abstract |
Background |
Interaction between lymphocytes and structural cells has been proposed as a key factor in regulating inflammation in asthma.
Objective |
This study was designed to investigate the effect of epithelial cells and fibroblasts on T-lymphocyte survival by using a 3-dimensional tissue-engineered model.
Methods |
Engineered human bronchial mucosal tissues were produced by using fibroblasts, epithelial cells, and autologous T cells from asthmatic and healthy donors. T-cell apoptosis and apoptotic marker expression by T cells were evaluated by using the terminal deoxynucleotidyl transferase biotinylated d-UTP nick end-labeling technique and immunofluorescence, respectively. Cytokines implicated in T-cell survival were measured by means of ELISA in culture supernatants.
Results |
We demonstrated histologically that we were able to generate a well-structured engineered bronchial mucosa by using epithelial cells, fibroblasts, and T cells cultured from healthy and asthmatic subjects. Structural cells from asthmatic subjects cultured in this model induced a significant decrease in the ability of T cells to undergo apoptosis represented by a decrease in DNA fragmentation and proapoptotic molecule expression (Bcl-2–associated X protein and Fas ligand). Structural cells from healthy control subjects have no effect. Among cytokines measured in the supernatants, only TGF-β1 was significantly increased in the model derived from cells of asthmatic subjects.
Conclusion |
These results support the concept that bronchial structural cells might play a critical role in the regulation of inflammation in asthma by increasing the survival of T lymphocytes. The results also further validated the model as a tool for investigating the interaction between inflammatory and structural cells.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, apoptosis, T cells, engineered human bronchial mucosa, cytokines
Abbreviations used : Bax, EHBM, FasL, PI, TUNEL
Plan
| Supported by the Canadian Institutes of Health Research (CIHR) and the Canadian Asthma Society. |
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| Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 121 - N° 3
P. 692-699 - mars 2008 Retour au numéro
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