Cyanidin-3-O-β-glucoside ameliorates lipopolysaccharide-induced acute lung injury by reducing TLR4 recruitment into lipid rafts.
Cyanidin-3-O-β-glucoside (C3G), a typical anthocyanin pigment that exists in the human diet, has been reported to have anti-inflammatory properties. The aim of this study was to detect the effect of C3G on LPS-induced acute lung injury and to investigate the molecular mechanisms. Acute lung injury was induced by intratracheal administration of LPS in mice. Alveolar macrophages from mice were stimulated with LPS and were treated with C3G. Our results showed that C3G attenuated lung histopathologic changes, myeloperoxidase (MPO) activity, TNF-α, IL-1β and IL-6 production in LPS-induced acute lung injury model. In vitro, C3G dose-dependently inhibited TNF-α, IL-1β, IL-6, IL-10 and IFN-β production, as well as NF-κB and IRF3 activation in LPS-stimulated alveolar macrophages. Furthermore, C3G disrupted the formation of lipid rafts by depleting cholesterol and inhibited TLR4 translocation into lipid rafts. Moreover, C3G activated LXRα-ABCG1-dependent cholesterol efflux. Knockout of LXRα abrogated the anti-inflammatory effects of C3G. In conclusion, C3G has a protective effect on LPS-induced acute lung injury. The promising anti-inflammatory mechanisms of C3G is associated with up-regulation of the LXRα-ABCG1 pathway which result in disrupting lipid rafts by depleting cholesterol and reducing translocation of TLR4 to lipid rafts, thereby suppressing TLR4 mediated inflammatory response.
['Fu|Yunhe|Y|', 'Zhou|Ershun|E|', 'Wei|Zhengkai|Z|', 'Wang|Wei|W|', 'Wang|Tiancheng|T|', 'Yang|Zhengtao|Z|', 'Zhang|Naisheng|N|']
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 D018528:ATP-Binding Cassette Transporters D055371:Acute Lung Injury D000818:Animals D000872:Anthocyanins D001692:Biological Transport D002478:Cells, Cultured D002784:Cholesterol D005786:Gene Expression Regulation D005960:Glucosides D050838:Interferon Regulatory Factor-3 D016899:Interferon-beta D016753:Interleukin-10 D053583:Interleukin-1beta D015850:Interleukin-6 D007442:Intubation, Intratracheal D008070:Lipopolysaccharides D008074:Lipoproteins D000071518:Liver X Receptors D016676:Macrophages, Alveolar D008297:Male D021962:Membrane Microdomains D051379:Mice D016328:NF-kappa B D057093:Orphan Nuclear Receptors D009195:Peroxidase D015398:Signal Transduction D051197:Toll-Like Receptor 4 D014409:Tumor Necrosis Factor-alpha
Cyanidin-3-O-β-glucoside TLR4 Lipid raft ABCG1 LXR