HDL, ABCA1 and ABCG1 transporters in cholesterol efflux and immune responses

HDL promotes cholesterol efflux via ABCA1 and ABCG1 and these transporters modulate the fluidity of the plasma membrane as well lipid raft formation. This, in turn, modulates the Toll-like receptor 4 signaling pathway by lipopolysaccharide (LPS) involving the formation of a LPS complex in lipid raft consisting of surface molecules such as CD14 and MD2. ABCG1 has a more potent role in modulating macrophage inflammatory response than ABCA1 but maximal effects require the activity of both transporters, suggesting complementary roles of these transporters. This response was not specific of TLR4 since deficiency of ABCA1 and ABCG1 also enhanced other Toll-like receptor signaling such as TLR2 present at the cell surface. Subsequently, downstream signaling molecule such as Myd88 will control the activation of NF-κB and the inflammatory gene expression response. Activation of LXR can modulate the infammatory response through transrepression of NF-κB but this mechanism doesn’t seem to be controlled by ABCA1 or ABCG1 activity. Free cholesterol accumulation in the endosomal compartment also modulated the inflammatory response by spontaneous activation of Toll-like receptors present in this compartment such as TLR3. By promoting cholesterol efflux from the late endosome compartment, ABCA1 may have a unique role in dampening inflammation.

Publication

The role of HDL, ABCA1 and ABCG1 transporters in cholesterol efflux and immune responses. () Laurent Yvan-Charvet, et al. Arterioscler Thromb Vasc Biol. ;30(2):139-143. Figure: F1. Homo sapiens

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