title: Ganglioside GD1a suppresses LPS-induced pro-inflammatory cytokines in RAW264.7 macrophages by reducing MAPKs and NF-κB signaling pathways through TLR4.
abstract: Gangliosides, sialic acid-containing glycosphingolipids, have been considered to be involved in the development, differentiation, and function of nervous systems in vertebrates. However, the mechanisms for anti-inflammation caused by gangliosides are not clear. In this paper, we investigated the anti-inflammation effects of ganglioside GD1a by using RAW264.7 macrophages. Our data demonstrated that treatment of macrophages with lipopolysaccharide significantly increased the production of NO and pro-inflammatory cytokines. GD1a suppressed the induction of iNOS and COX-2 mRNA and protein expression and secretory pro-inflammatory cytokines in culture medium, such as TNFα, IL-1α and IL-1β. In addition, LPS-induced phosphorylation of mitogen-activating protein kinases and IκBα degradation followed by translocation of the NF-κB from the cytoplasm to the nucleus were attenuated after GD1a treatment. Furthermore, GD1a probably inhibited LPS binding to macrophages and LPS-induced accumulation between TLR4 and MyD88. Taken together, the results demonstrated that ganglioside GD1a inhibited LPS-induced inflammation in RAW 264.7 macrophages by suppressing phosphorylation of mitogen-activating protein kinases and activation of NF-κB through repressing the Toll-like receptor 4 signaling pathway.
authors.affiliation: School of Life Science, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors.forename: Yiren
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Life Science, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Cui
authors.affiliation: School of Life Science, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors.forename: Fayang
authors.initials: F
authors.lastname: Cao
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Qin
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Medical Devices, Shenyang Pharmaceutical University, 117004 Benxi, PR China. Electronic address: zhangjinghai@syphu.edu.cn.
authors.forename: Jinghai
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D005732:Gangliosides / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010766:Phosphorylation; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D005732:Gangliosides; D008070:Lipopolysaccharides; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C021298:ganglioside, GD1a; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone
keywords: Anti-inflammation; Ganglioside GD1a; Mitogen-activated protein kinases; Nuclear factor-kappa B; Toll-like receptor 4