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TGF-1 downregulates CFTR expression and function in nasal polyps of non-CF patients

¹Institut National de la Santé et de la Recherche Médicale, unité 492, Faculté de médecine Paris XII, Créteil; ²Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Hôpitaux Henri Mondor (Assistance Publique-Hôpitaux de Paris) et Intercommunal, Créteil; ³Institut National de la Santé et de la Recherche Médicale, unité 468, Hôpital Henri Mondor, Créteil; ⁴Laboratoire de Cytophysiologie et Toxicologie cellulaire, Université Paris VII; ⁵Institut National de la Santé et de la Recherche Médicale, unité 467, Faculté de médecine Paris V, Paris; and ⁶Département de Génétique, Cytogénétique et Embryologie, Groupe Hospitalier Pitié-Salpêtrière (Assistance Publique-Hôpitaux de Paris), Paris, France

Submitted 17 February 2004 ; accepted in final form 17 August 2004

Nasal polyposis is a chronic inflammatory disease of the upper airways. It has been suggested that ion transports and CFTR expression could be modified in epithelial cells from nasal polyps of non-cystic fibrosis patients. We compared human nasal epithelial cells from nasal polyps (NP) with control nasal mucosa (CM). The level of CFTR mRNA was studied by Northern blot analysis and protein expression was studied by immunoprecipitation both ex vivo and in vitro in primary cultures of human nasal epithelial cells at the air-liquid interface. Ion transports were evaluated by short-circuit measurements in vitro. CFTR gene and protein expressions were significantly decreased in NP native tissues and in culture on day 4, when a global defect of ion transports was observed in NP cultures, but not in CM. We evaluated the effect of transforming growth factor (TGF)-1 on CFTR expression and function in NP cultures on day 14 and showed, for the first time, that TGF-1 was able to significantly downregulate the level of CFTR mRNA and cAMP-dependent current in NP cultures. Finally, we showed that the effects of TGF-1 on ion transports could be reversed after 48-h removal of TGF-1 in NP cultures. In conclusion, our data strongly suggest that chronic inflammation in nasal polyposis downregulates CFTR gene and protein expression.

inflammation; transforming growth factor-1; respiratory epithelium; ion transport; primary culture