Effect of Th2 type cytokines on hCLCA1 and mucus expression in cystic fibrosis airways.

Correlations between expression of interleukin (IL)-9, the calcium-activated chloride channel hCLCA1 and mucus expression in cystic fibrosis (CF) airways have suggested a causal relationship. To verify this hypothesis mucosal tissue from upper airways of CF patients (N=5) was stimulated with the Th2 type cytokines IL-4, IL-9, or IL-13. Expression of hCLCA1 mRNA and protein as well as mucus and mucin (MUC5AC) gene expression was quantified using real time PCR, immunohistochemistry (hCLCA1) and PAS staining (mucus). Th2 type cytokines significantly increased hCLCA1 protein expression (P<0.05) whereas increase in hCLCA1 mRNA expression failed to reach statistical significance (P>0.05). Mucin protein and MUC5AC mRNA expression were not significantly changed (P>0.05). These data suggest that Th2 type cytokines may increase hCLCA1 expression in CF but may not have a significant effect on mucus expression. Therefore the role of hCLCA1 as a mediator of mucus overexpression in CF has to be questioned.