β1, β2, and β3 adrenoceptors and Na+/H + Exchanger Regulatory Factor 1 expression in human bronchi and their modifications in cystic fibrosis

Florian Bossard, Émilie Silantieff, Emmanuelle Lavazais-Blancou, Amal Robay, Christine Sagan, Bertrand Rozec, Chantal Gauthier

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12 Citations (Scopus)

Abstract

To date, three b-adrenoceptor (b-AR) subtypes have been identified, but only β1-ARs and β2-ARs have been characterized in human lungs. Moreover, β2-ARs physically interact with the cystic fibrosis transmembrane conductance regulator (CFTR) through the Na +/H+ Exchanger Regulatory Factor 1 (NHERF1) protein.β3-ARs, which stimulate CFTR activity in transfected cells, have not been identified in human lungs. This study aimed (1) to characterize the presence of b-AR subtypes, especiallyβ3-AR, in human bronchi, and (2) to compare their expression as well as that of NHERF1 in non-cystic fibrosis (CF) versus advanced CF lung samples. In human non-CF bronchi, β1-AR, β2-AR,β3-AR, and NHERF1 transcripts and proteins were expressed mainly in bronchial epithelial cells. Those results were strengthened by the native expression of β1-AR, β2-AR, andβ3- AR in a human epithelial cell line, 16HBE14o2. All b-AR subtypes stimulated CFTR activity. In CF bronchi, we demonstrated β1-AR and b3-AR overexpression, and NHERF1 and β2-AR underexpression. The origin of this protein remodeling (involving the physical or functional absence of CFTR, infection, inflammation, or high adrenergic tone) deserves further investigation. These results evidence for the first time, to the best of our knowledge, the presence ofβ3-ARs in human bronchi, and suggest their usefulness as a putative new pharmacologic target in lung diseases where fluid homeostasis is altered. Furthermore, NHERF1 may be a new therapeutic target in patients with CF, to facilitate the trafficking of mutated CFTR to plasma membrane.

Original languageEnglish
Pages (from-to)91-98
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume44
Issue number1
DOIs
Publication statusPublished - 1 Jan 2010

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Keywords

  • Bronchus
  • Cystic fibrosis
  • Epithelium
  • NHERF1
  • β-adrenergic receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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