Lipopolysaccharide Increases the Expression of Multidrug Resistance-Associated Protein 1 (ABCC1) in Macrophages

Abstract

Multidrug resistance-associated protein 1 (MRP-1) is a ubiquitously expressed member of the ATP-binding cassette transporter family. MRP-1 is one of the primary transporters of glutathione and glutathione conjugates. This protein also transports antiretroviral therapeutics, such as HIV-1 protease inhibitors (PI). We hypothesized that inflammatory mediators that activate macrophages would modify the expression and activity of MRP-1 in macrophages. Real time PCR assays western blots and calcein efflux assays were used to show that exposure of macrophage cell line RAW 264.7 to LPS increased expression of MRP-1 at the level of mRNA and protein, as well as at the level of functional activity. Treatment of macrophages with LPS resulted in 2-fold increases of MRP-1 expression or functional activity. LPS-mediated increases in calcein efflux were repressed by the MRP-specific inhibitor MK-571. These results suggest that the effectiveness of HIV-1 PI therapy may be compromised by the presence of opportunistic infections.