TY - JOUR T1 - Differential Regulation of Cystic Fibrosis Transmembrane Conductance Regulator by Interferon γ in Mast Cells and Epithelial Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 563 LP - 570 DO - 10.1124/jpet.105.087528 VL - 315 IS - 2 AU - Marianna Kulka AU - Rene Dery AU - Drew Nahirney AU - Marek Duszyk AU - A. Dean Befus Y1 - 2005/11/01 UR - http://jpet.aspetjournals.org/content/315/2/563.abstract N2 - 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 interferon γ (IFNγ) down-regulated CFTR expression in epithelial cells (T84), but by contrast, we found that IFNγ up-regulated CFTR mRNA and protein expression in rat and human mast cells. IFNγ up-regulation of CFTR in mast cells was inhibited by p38 and extracellular signal-regulated kinase (ERK) kinase inhibitors but not a Janus tyrosine kinase (JAK)2 inhibitor, whereas in T84 cells IFNγ-mediated down-regulation of CFTR was JAK2-dependent and ERK- and p38-independent. Furthermore, IFNγ down-regulation of CFTR in T84 epithelial cells was STAT1-dependent, but up-regulation of CFTR in mast cells was STAT1-independent. Thus, differential regulatory pathways of CFTR expression in mast cells and epithelial cells exist that depend upon either p38/ERK or JAK/STAT pathways, respectively. Surprisingly, IFNγ treatment of mast cells inhibited Cl- efflux, in contrast to up-regulation of CFTR/mRNA and protein expression. However, down-regulation of Cl- flux correlated with IFNγ-mediated inhibition of mediator secretion. This and other work suggests that the effect of IFNγ on CFTR expression in mast cells is important for their function. The American Society for Pharmacology and Experimental Therapeutics ER -