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β2-Agonist modulates epithelial gene expression involved in the T- and B-cell chemotaxis and induces airway sensitization in human isolated bronchi

AuthorsFaisy, Christopher; Pinto Pérez, Francisco M. CSIC ORCID; Blouquit-Laye, Sabine; Danel, Claire; Naline, Emmanuel; Buenestado, Amparo; Grassin-Delyle, Stanislas; Burgel, Pierre-Régis; Chapelier, Alain; Advenier, Charles; Candenas, M. Luz CSIC ORCID; Devillier, Philippe
Airway epithelial cell
Gene expresion
Airway sensitization
Issue DateFeb-2010
CitationPharmacological Research 61(2): 121-128 (2010)
AbstractRegular use of β2-adrenoceptor agonists may enhance non-specific airway responsiveness and inflammation. In earlier experimental studies, we showed that prolonged in vitro fenoterol exposure induced airway sensitization via perturbed epithelial regulation of bronchoconstriction. The aim of the present work was to examine the involvement of inflammatory mediator genes and proinflammatory cells and to investigate the role of the bronchial epithelium in these untoward effects. Bronchial tissues were surgically removed from 17 ex-smokers. Bronchial rings and primary cultures of bronchial epithelial cells were incubated with 0.1 μM fenoterol for 15 h. Levels of mRNA-expression were analyzed using a real-time quantitative reverse transcription-polymerase chain reaction array. Bronchial rings were contracted with endothelin-1 and immune cell infiltration was assessed by immunohistochemistry. Compared to paired controls, fenoterol up-regulated the mRNAs of cytokines/proteins implicated in the recruitment of T and B cells or the activation and proliferation of bronchial epithelial cells (CCL20/MIP-3α, FOXA2, PPAR-γ) in isolated bronchi and in cultured epithelial cells. Fenoterol exposure significantly enhanced CD8+-T and differentiated CD138+-B-cells infiltration into the bronchi, especially the subepithelial area. Increase in CD8 or CD138 labeling-intensity strongly correlated with rise in maximal contraction to endothelin-1 induced by fenoterol exposure. In summary, our results show that fenoterol modulates the T and B cells chemotaxis possibly via the epithelial chemokine secretion in isolated bronchi from ex-smokers. They also suggest that the infiltration of resident T and B cells into the subepithelial area is associated with an increase in airway responsiveness due to fenoterol exposure.
Description8 páginas, 6 figuras, 1 tabla.
Publisher version (URL)http://dx.doi.org/10.1016/j.phrs.2009.08.003
Appears in Collections:(IIQ) Artículos
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