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Lipopolysaccharide Increases the Expression of Multidrug Resistance-Associated Protein 1 (ABCC1) in Macrophages
Silverstein, Peter S. Audus, Kenneth L. Qureshi, Nilofer Kumar, Anil
Silverstein, Peter S.
Audus, Kenneth L.
Qureshi, Nilofer
Kumar, Anil
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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.
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2010-12
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Springer Verlag
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Silverstein, P. S., Audus, K. L., Qureshi, N., & Kumar, A. (2010). Lipopolysaccharide Increases the Expression of Multidrug Resistance-Associated Protein 1 (ABCC1) in Macrophages. Journal of Neuroimmune Pharmacology : The Official Journal of the Society on NeuroImmune Pharmacology, 5(4), 516–520. http://doi.org/10.1007/s11481-009-9180-4