The objective of this study was to determine the expression and activity of multidrug resistance-associated protein (MRP1) in a human airway epithelial cell line (Calu-1) and to further assess whether budesonide, a potent antiasthma corticosteroid, alters the expression and activity of MRP1 in these cells. Reverse transcriptase polymerase chain reaction (RT-PCR) and the Western blot analysis demonstrated the MRP1 mRNA and MRP1 protein in Calu-1 cells. Indomethacin, probenecid, and verapamil significantly enhanced the fluorescein accumulation and reduced the fluorescein efflux, consistent with the MRP1 activity in the Calu-1 cells. Following 14-day budesonide treatment, fluorescein accumulation increased and fluorescein efflux decreased, consistent with the inhibition of MRP1 activity by budesonide. At a concentration (10 microM) devoid of cytotoxicity, budesonide treatment decreased MRP1 mRNA and MRP1 protein expression in Calu-1 cells by 38% and 42%, respectively. In addition, budesonide (10 microM) enhanced the sensitivity of the MRP1 overexpressing COR-L23R cells to vincristine, suggesting the chemosensitizing effect of budesonide. Thus, budesonide inhibits MRP1 expression and may be useful as a chemosensitizer in tumor chemotherapy.