Increased cellular free cholesterol in macrophage-specific Abca1 knock-out mice enhances pro-inflammatory response of macrophages
作者： Xuewei Zhu , Ji-Young Lee , Jenelle M. Timmins , J. Mark Brown , Elena Boudyguina
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摘要: Macrophage-specific Abca1 knock-out (Abca1–M/–M) mice were generated to determine the role of macrophage ABCA1 expression in plasma lipoprotein concentrations and innate immune response macrophages. Plasma lipid chow-fed Abca1–M/–M wild-type (WT) indistinguishable. Compared with WT macrophages, macrophages had a >95% reduction protein, failed efflux apoA-I, significant increase free cholesterol (FC) membrane rafts without induction endoplasmic reticulum stress. Lipopolysaccharide (LPS)-treated exhibited enhanced pro-inflammatory cytokines increased activation NF-κB MAPK pathways, which could be diminished by silencing MyD88 or chemical inhibition MAPK. In vivo LPS injection also resulted higher compared mice. Furthermore, depletion methyl-β-cyclodextrin normalized FC content between two genotypes their LPS; repletion cellular accumulation LPS. Our results suggest that may protect against atherosclerosis facilitating net removal excess from dampening MyD88-dependent signaling pathways cell raft content.
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