Cystic fibrosis and normal fibroblasts have identical glucocorticoid receptor profiles and induced protein responses.

Abstract

The possibility of differences in glucocorticoid sensitivity between normal and cystic fibrosis fibroblasts was studied in cultured cells derived from forearm skin biopsies. Both normal and cystic fibrosis cells bound tritiated dexamethasone with high affinity (Kd 37 degrees C approximately equal to 10 nmol/1) to a limited class of sites (concentration approximately equal to 50,000/cell); no difference between cystic fibrosis and normal cells was seen in the nuclear transfer of receptor-bound tritiated dexamethasone. After 4 h exposure to dexamethasone and analysis of 35S-methionine labelled proteins by 2-dimensional gel electrophoresis, both normal and cystic fibrosis cells showed increased abundance of protein kappa (molecular weight approximately equal to 41,000; pKi approximately equal to 6.5) over non-steroid exposed gels. After 16 h exposure, in both cystic fibrosis and normal cells exposed to dexamethasone a decrease in protein omega (mol. wt approximately equal to 42,000; pKi approximately equal to 5.4) was seen compared with control. We interpret these data as evidence against a difference in glucocorticoid receptor of effector mechanisms between cystic fibrosis and normal fibroblasts.