Ganglioside GD1a suppresses LPS-induced pro-inflammatory cytokines in RAW264.7 macrophages by reducing MAPKs and NF-κB signaling pathways through TLR4

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 GDla 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 TNF alpha, IL-1 alpha and IL-1 beta. In addition, LPS-induced phosphorylation of mitogen-activating protein kinases and I kappa B alpha degradation followed by translocation of the NF-kappa B from the cytoplasm to the nucleus were attenuated after GDla 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 Idnases and activation of NF-kappa B through repressing the Toll-like receptor 4 signaling pathway. (C) 2015 Elsevier B.V. All rights reserved.