Ganglioside GM3 suppresses lipopolysaccharide‐induced inflammatory responses in rAW 264.7 macrophage cells through NF‐κB,AP‐1, and MAPKs signaling |
| |
Authors: | Junyoung Park Choong‐Hwan Kwak Sun‐Hyung Ha Kyung‐Min Kwon Fukushi Abekura Seung‐Hak Cho Young‐Chae Chang Young‐Choon Lee Ki‐Tae Ha Tae‐Wook Chung Cheorl‐Ho Kim |
| |
Institution: | 1. Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sungkyunkwan University, Seoburo, Jangan‐Gu, Suwon, Gyunggi‐Do, Republic of Korea;2. Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan City, Gyeongsangnam‐Do, Republic of Korea;3. Research Institute, Davinch‐K Co., Ltd, Geumcheon‐Gu, Seoul, Republic of Korea;4. Division of Enteric Diseases, Center for Infectious Diseases Research, Korea National Institute of Health, Heungdeok‐gu, Cheongju, Republic of Korea;5. Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea;6. Faculty of Medicinal Biotechnology, Dong‐A University, Saha‐Gu, Busan, Republic of Korea |
| |
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. |
| |
Keywords: | ganglioside GM3 inflammation LPS RAW 264 7 cells |
|
|