Lipopolysaccharide increases the expression of multidrug resistance-associated protein 1 (MRP1) in RAW 264.7 macrophages.
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 lipopolysaccharide (LPS) increased expression of MRP-1 at the levels of mRNA, protein, and 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.
Silverstein
Peter S
PS
Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA. Silversteinp@umkc.edu
Audus
Kenneth L
KL
Qureshi
Nilofer
N
Kumar
Anil
A
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008070:Lipopolysaccharides; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C421109:multidrug resistance-associated protein 1