Objective and design: To investigate the regulation of cholesterol transporters, including ATP-binding cassette transporter A1 (ABCA1), ABCG1 and scavenger receptor class B, type I (SR-BI), by inflammatory stimuli in macrophages. MATERIALS AND TREATMENTS: RAW 264.7 macrophages and mouse peritoneal macrophages were treated with inflammatory stimuli with or without rosiglitazone, a peroxisome proliferator activated receptor γ (PPARγ) agonist, or T0901317, a liver X receptor (LXR) agonist.
Methods: Real-time PCR and Western blotting for cholesterol transporters as well as cellular cholesterol efflux to high-density lipoprotein 2 (HDL(2)) were determined.
Results: In RAW 264.7 macrophages, lipopolysaccharide (LPS) significantly reduced ABCG1 and PPARγ as well as cholesterol efflux to HDL(2). Rosiglitazone and T0901317 induced ABCA1 and ABCG1 several-fold, but LPS reduced only ABCG1. ABCG1 and SR-BI proteins, but not ABCA1, were decreased by LPS. In mouse peritoneal macrophages, LPS, tumor necrosis factor α and interleukin-1β decreased ABCG1, SR-BI, LXRα and PPARγ mRNA. The agonists increased ABC transporter expression but LPS reduced mRNA of T0901317-induced ABCA1 as well as basal and agonists-induced ABCG1. SR-BI protein was increased by rosiglitazone but LPS decreased the levels.
Conclusion: The data suggest that inflammatory insults repress ABCG1 and SR-BI expression partly dependent on PPARγ with a minimal effect on ABCA1 expression.