Bacterial lipopolysaccharide induces expression of ABCA1 but not ABCG1 via an LXR-independent pathway

Abstract

Two ATP-binding cassette transporter proteins, ABCA1 and ABCG1, may mediate an active efflux of cellular cholesterol and phospholipids. They are ubiquitously expressed and are subject to regulation by cholesterol loading or by treatment with agents that activate the nuclear hormone receptor LXR. Earlier studies in both primates and non-primates reported that treatment with endotoxin (bacterial lipopolysaccharide, LPS) reduces plasma levels of HDL cholesterol. To determine if such HDL reduction correlates with a change in ABCA1 or ABCG1 expression, their expressions were measured in THP-1 monocytes and mice treated with LPS. LPS treatment leads to a rapid, dosedependent increase of ABCA1 but not ABCG1 mRNA expression. Analysis of mouse livers showed that LPS treatment decreases expression of CYP7A, another target gene of LXR. When THP-1 cells were transfected with the ABCA1 promoter construct ( ؊ 928 to ؉ 101 bp), promoter activity was significantly increased by treatment of 22( R )hydroxycholesterol but not by LPS. Together, these studies show that LPS regulates ABCA1 expression through an LXR-independent mechanism. Further studies showed that treatment with Rhodobacter sphaeroiders LPS, an LPS antagonist, or PD169316, a specific p38 MAP kinase inhibitor, prevented the induction of ABCA1 by LPS. Therefore, this suggests that both transport of LPS from the plasma membrane to an intracellular site and activation of p38 MAP kinase are involved in the LPS-mediated induction of ABCA1. -Kaplan, R., X. Gan, J. G. Menke, S. D Wright, and T-Q. Cai. Bacterial lipopolysaccharide induces expression of ABCA1 but not ABCG1 via an LXR-independent pathway.

4-Octyl Itaconate and Dimethyl Fumarate Induce Secretion of the Anti-Inflammatory Protein Annexin A1 via NRF2

“…We found that LPS increased mRNA levels of Abca1 ( Fig. 4A ), which was previously reported in the literature ( 50 ). We hypothesized that perhaps NRF2 activation could be connected to secretion of annexin A1 via ABCA1 induction.…”

Oridonin attenuates atherosclerosis by inhibiting foam macrophage formation and inflammation through FABP4/PPARγ signalling

“…Interestingly, our result demonstrated that the expression of ABCG1 had no response to oridonin stimulation, which was not parallel with ABCA1. This phenomenon might be due to the underlying difference between ABCA1 and ABCG1, which was consistent with other groups' finding 31–33 . Thus, the beneficial effect of oridonin on lipid accumulation in macrophages might be contributed to the LXRα‐induced ABCA1 up‐regulation, but not ABCG1.…”

“…This phenomenon might be due to the underlying difference between ABCA1 and ABCG1, which was consistent with other groups' finding. 31 , 32 , 33 Thus, the beneficial effect of oridonin on lipid accumulation in macrophages might be contributed to the LXRα‐induced ABCA1 up‐regulation, but not ABCG1.…”

Participation of ABCA1 Transporter in Pathogenesis of Chronic Obstructive Pulmonary Disease

“…The regulation of the transporter expression is probably carried out via the PPARa (peroxisomeproliferator-activated receptor-a)/RXR pathway [135]. Previously it has been found out that the effect of LPS on macrophages leads to a rapid dose-dependent increase in the expression of ABCA1 mRNA [180]. It has also been shown that infection Chlamydia pneumoniae infection reduces ABCA1 expression in A549 lung epithelial carcinoma cells [66].…”