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.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
Yunhe
Y
Fu
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
Ershun
E
Zhou
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
Zhengkai
Z
Wei
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
Wei
W
Wang
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
Tiancheng
T
Wang
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China. Electronic address: yangzhengtao01@sina.com.
Zhengtao
Z
Yang
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China. Electronic address: zhangns61@sohu.com.
Naisheng
N
Zhang
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology; D055371:Acute Lung Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol; D005786:Gene Expression Regulation; D005960:Glucosides / Q000494:pharmacology*; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007442:Intubation, Intratracheal; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology; D000071518:Liver X Receptors; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D021962:Membrane Microdomains; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D009195:Peroxidase / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000872:Anthocyanins; D005960:Glucosides; C556062:IL10 protein, mouse; D050838:Interferon Regulatory Factor-3; D053583:Interleukin-1beta; D015850:Interleukin-6; C494233:Irf3 protein, mouse; D008070:Lipopolysaccharides; D008074:Lipoproteins; D000071518:Liver X Receptors; D016328:NF-kappa B; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C462279:cyanidin-3-O-beta-glucopyranoside; D016753:Interleukin-10; D016899:Interferon-beta; D002784:Cholesterol; D009195:Peroxidase
ABCG1; Cyanidin-3-O-β-glucoside; LXR; Lipid raft; TLR4