Ganglioside GM3 suppresses lipopolysaccharide‐induced inflammatory responses in rAW 264.7 macrophage cells through NF‐κB, AP‐1, and MAPKs signaling. Issue 1 (23rd August 2017)

• Record Type: Journal Article
• Authors: Park, Junyoung; Kwak, Choong‐Hwan; Ha, Sun‐Hyung; Kwon, Kyung‐Min; Abekura, Fukushi; Cho, Seung‐Hak; Chang, Young‐Chae; Lee, Young‐Choon; Ha, Ki‐Tae; Chung, Tae‐Wook; Kim, Cheorl‐Ho
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 1(2018)
• Page Start: 1173
• Page End: 1182
• Publication Date: 2017-08-23
• Subjects: ganglioside -- GM3 -- inflammation -- LPS -- RAW 264.7 cells; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26287
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Gangliosides are known to specifically inhibit vascular leukocyte recruitment and consequent interaction with the injured endothelium, the basic inflammatory process. In this study, we have found that the production of nitric oxide (NO), a main regulator of inflammation, is suppressed by GM3 on murine macrophage RAW 264.7 cells, when induced by LPS. In addition, GM3 attenuated the increase in cyclooxyenase‐2 (COX‐2) protein and mRNA levels in lipopolysaccharide (LPS)‐activated RAW 264.7 cells in a dose‐dependent manner. Moreover, GM3 inhibited the expression and release of pro‐inflammatory cytokines of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1β (IL‐1β) in RAW 264.7 macrophages. At the intracellular level, GM3 inhibited LPS‐induced nuclear translocation of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) and activator protein (AP)‐1 in RAW 264.7 macrophages. We, therefore, investigated whether GM3 affects mitogen‐activated protein kinase (MAPK) phosphorylation, a process known as the upstream signaling regulator. GM3 dramatically reduced the expression levels of the phosphorylated forms of ERK, JNK, and p38 in LPS‐activated RAW 264.7 cells. These results indicate that GM3 is a promising suppressor of the vascular inflammatory responses and ganglioside GM3 suppresses the LPS‐induced inflammatory response in RAW 264.7 macrophages by suppression of NF‐κB, AP‐1, and MAPKs signaling. Accordingly, GM3 is suggested as a beneficial agent for the treatment of diseases that are associated with inflammation. Abstract : Ganglioside GM3 Suppresses Lipopolysaccharide‐Induced Inflammatory Responses In RAW 264.7 Macrophage Cells Through NF‐κB, AP‐1 And MAPKs Signaling. Accordingly, GM3 is suggested as a beneficial agent for the treatment of diseases that are associated with inflammation.