The Liver X Receptor Is Upregulated in Monocyte-Derived Macrophages and Modulates Inflammatory Cytokines Based on LXRα Polymorphism

Figure 5

Toll-like receptor 7 (TLR7) and TLR9 inhibitors attenuate proinflammatory cytokine responses by liver X receptor (LXR) agonists in human TLR-stimulated monocyte-derived macrophages, especially in LXRα -1830 TC genotype-transfected U937 cells. mRNA expression of LXRα, ABCA1, and several cytokines was measured by quantitative real-time PCR. (a) Treatment with TLR7 inhibitors after stimulating with TLR ligands CL097 (TLR7/8). (b) Treatment with TLR9 inhibitors after stimulating with TLR ligands ODN (TLR9). (c) Dose response of TLR9 inhibitors in the presence of LXR agonist (T0901317 or GW3965) for 24 hrs. Data are shown from three independent experiments. Values are the means and SD. vs. controls. The data obtained upon treatment of the cells with TLR9 inhibitor were similar to those obtained for the TLR7 inhibitor (Figure 5(b)). The TLR9 inhibitor decreased the levels of IL-1β, TNF-α, COX-2, and IFN-γ in U937 cells treated with PMA for 24 h prior to stimulation with TLR ligand ODN. The levels of proinflammatory cytokines were increased in both TC and TT genotype-transfected cells, stimulated with ODN, but especially increased in TC genotype-transfected U937 cells compared to those in TT genotype-transfected macrophages. Furthermore, treatment with TLR9 inhibitor (more than 1 μM) significantly decreased the levels of IL-1β, TNF-α, COX-2, and IFN-γ in TC genotype-transfected U937 cells stimulated with LXR ligand (T0901317), and those of TNF-α, COX-2, and IFN-γ in TT genotype-transfected U937 cells (Figure 5(c)).

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