RT-PCR analysis of ABC, SLC and SLCO drug transporters in human lung epithelial cell models

Abstract

Carrier-mediated transport mechanisms play crucial roles in drug absorption and elimination processes, as well as in the transport of endogenous molecules affecting cellular regulation and function. In this study we used RT-PCR analysis to characterise the mRNA transcript expression of a wide range of membrane carrier transporters in several in-vitro lung epithelial cell models. Transporters studied included: 11 ATP-binding cassette (ABC) transporters, 11 solute carrier (SLC) transporters and 9 solute carrier organic anion (SLCO) transporters. The cell culture models included both established cell lines (A549, Calu-3, 16HBE14o-, BEAS-2B) and freshly isolated lung epithelial cells in primary culture (human bronchial and alveolar epithelial cells). The expression profiles of several clinically relevant drug transporters were characterised using RT-PCR analysis. Our results showed differential transporter expression in cell culture models from different regions of the lung and also highlighted disparities when comparing lung cell lines with primary cell culture models. Differences in transporter expression between cell models of pulmonary and gastrointestinal origin were also noted. The information will guide and validate the use of in-vitro lung epithelial cell lines in the study of pulmonary administered drugs and candidate molecules.