CFTR AND DIFFERENTIATION MARKERS EXPRESSION IN NON-CF AND DELTA-F-508HOMOZYGOUS CF NASAL EPITHELIUM

Human nasal polyps from non-CF and Delta F 508 homozygous CF patients were used to compare the expression of CFTR and markers of epithelial differentiation, such as cytokeratins (CK) and desmoplakins (DP), at t he transcriptional and translational levels, mRNA expression was asses sed by semiquantitative RT/PCR kinetic assays while the expression and distribution of proteins were evaluated by immunofluorescence analysi s, In parallel, for each nasal tissue specimen, the importance of surf ace epithelium remodeling and inflammation was estimated after histolo gical observations, Our results show that the steady-state levels of C FTR, CK13, CK18, CK14, or DP 1 mRNA transcripts in Delta F 508 CF nasa l polyps were not significantly different from those of non-CF tissues , A variability in the CFTR mRNA transcript level and in the pattern o f CFTR immunolabeling has been observed between the different tissue s amples, However, no relationship was found between the level of CFTR m RNA transcripts and the CFTR protein expression and distribution, eith er in the non-CF or in the CF group, The histological observations of non-CF and CF nasal polyp tissue indicated that the huge variations in the expression and distribution of the CFTR protein were associated w ith the variations in the degree of surface epithelium remodeling and inflammation in the lamina propria, A surface epithelium, showing a sl ight basal cell hyperplasia phenotype associated with diffuse inflamma tion, was mainly characterized by a CFTR protein distribution at the a pex of ciliated cells in both non-CF and CF specimens. In contrast, in a remodeled surface epithelium associated with severe inflammation, C FTR protein presented either a diffuse distribution in the cytoplasm o f ciliated cells, or was absent, These results suggest that abnormal e xpression and distribution of the CFTR protein in CF airways is not on ly caused by CFTR mutations, Airway surface epithelium remodeling and inflammation could play a critical role in the posttranscriptional and /or the posttranslational regulation of the CFTR protein expression in non-CF and CF airways.