Submitted on February 17, 2004
Accepted on August 17, 2004
TGF
1 downregulates CFTR expression and function in nasal polyps of non-CF patients
Virginie Pruliere-Escabasse1, Pascale Fanen2, Anne Catherine Dazy3, Emmanuele Lechapt-Zalcman4, Dominique Rideau4, Aleksander Edelman5, Estelle Escudier6, and Andre Coste1*
1 Oto-Rhino-Laryngologie, Hopital Henri Mondor (Assistance Publique-Hopitaux de Paris) et Intercommunal de Creteil, Creteil, France; Faculte de Medecine Paris 12, Unite 492, Institut National de la Sante et de la Recherche Medicale, Creteil, France
2 Hopital Henri Mondor (Assistance Publique-Hopitaux de Paris), Unite 468, Institut National de la Sante et de la Recherche Medicale, Creteil, France
3 universite Paris 7, Laboratoire de Cytophysiologie et Toxicologie cellulaire, Paris, France
4 Oto-Rhino-Laryngologie, Hopital Henri Mondor (Assistance Publique-Hopitaux de Paris) et Intercommunal de Creteil, Creteil, France
5 Faculte de Medecine Paris 5, Unite 467, Institut National de la Sante et de la Recherche Medicale, Paris, France
6 Oto-Rhino-Laryngologie, Hopital Henri Mondor (Assistance Publique-Hopitaux de Paris) et Intercommunal de Creteil, Creteil, France; Depatment of Groupe Hospitalier Pitie-Salpetriere (Assistance Publique-Hopitaux de Paris), Departement de genetique, Cytogenetique et embryologie, Paris, France
* To whom correspondence should be addressed. E-mail: andre.coste{at}creteil.inserm.fr.
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 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 c-AMP dependent current in NP cultures. Finally, we showed that the effects of TGF-1 on ion transports could be reversed after 48h 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.
