Received for publication April 6, 2005.
Revised July 22, 2005.
Accepted for publication July 26, 2005.

Differential Regulation of CFTR by Interferon- in Mast Cells and Epithelial Cells

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent chloride channel in epithelial cells; recently we identified it in mast cells. Previous work that we confirmed showed that IFN downregulated CFTR expression in epithelial cells (T84), but by contrast, we found that IFN upregulated CFTR mRNA and protein expression in rat and human mast cells. IFN upregulation of CFTR in mast cells was inhibited by p38 and ERK kinase inhibitors but not a JAK2 inhibitor, whereas in T84 cells IFN-mediated downregulation of CFTR was JAK2 dependent, and ERK and p38 independent. Furthermore, IFN downregulation of CFTR in T84 epithelial cells was STAT1 dependent, but upregulation of CFTR in mast cells was STAT1 independent. Thus, differential regulatory pathways of CFTR expression in mast cells and epithelial cells exist that are dependent upon either p38/ERK or JAK/STAT pathways, respectively. Surprisingly, IFN treatment of mast cells inhibited Cl^- efflux, in contrast to upregulation of CFTR/mRNA and protein expression. However, downregulation of Cl^- flux correlated with IFN-mediated inhibition of mediator secretion. This and other work suggests that the effect of IFN on CFTR expression in mast cells is important for their function.

Key words: Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Epithelial Cells, Interferon gamma, Mast Cells, regulation