ReceptorIsoform.PDFVIP

0026-895X/06/6902-588–596 MOLECULAR PHARMACOLOGY Vol. 69, No. 2 U.S. Government work not protected by U.S. copyright 19679/3082568 Mol Pharmacol 69:588–596, 2006 Printed in U.S.A. CD38 Expression Is Insensitive to Steroid Action in Cells Treated with Tumor Necrosis Factor-? and Interferon-? by a Mechanism Involving the Up-Regulation of the Glucocorticoid Receptor ? Isoform Omar Tliba, John A. Cidlowski, and Yassine Amrani Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania (O.T., Y.A.); and Molecular Endocrinology Group, Laboratory of Signal Transduction, National Downloaded from Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (J.A.C.) Received October 6, 2005; accepted November 16, 2005 ABSTRACT Evidence shows that the CD38 molecule, recently involved in TNF? and IFN? impaired GC responsiveness by inhibiting ste- the two main features of asthma, bronchial hyper-responsive- roid induced both 1) GR?-DNA binding activity and 2) GC- ness and airway inflammation, could represent a new potential responsive element-(GRE)-dependent gene transcription. Al- therapeutic target for asthma. In this study, we investigated though levels of the GC receptor (GR) ? isoform remained whether glucocorticoid (GC), the most effective treatment for unchanged, expression of G