title: Glucosylceramide attenuates the inflammatory mediator expression in lipopolysaccharide-stimulated RAW264.7 cells.
abstract: The positive effect of glucosylceramide (GlcCer) on skin conditions is well known. Recently, there has been increasing interest in the potential antiinflammatory effects of GlcCer due to its efficacy in relieving atopic skin symptoms. However, the role of GlcCer in inflammation has not been investigated completely. Thus, we hypothesized that GlcCer might exhibit the antiinflammatory effects through the inhibition of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. To test this hypothesis, the antiinflammatory effects and signaling mechanisms of GlcCer were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. We report that GlcCer inhibited messenger RNA and protein expression of tissue necrosis factor α and interleukin 1β without cytotoxicity. However, it did not affect interleukin 6 production in LPS-stimulated RAW 264.7 macrophages. Glucosylceramide also suppressed prostaglandin E2 but not nitric oxide production, consistent with its inhibition of cyclooxygenase 2 but not of inducible nitric oxide synthase expression. The molecular mechanism of GlcCer-mediated inhibition of LPS-induced inflammation in RAW 264.7 cells is closely related to suppression of NF-κB p65 subunit nuclear translocation as well as to phosphorylation of extracellular signal-regulated kinase and, in particular, p38 MAPK. In addition, GlcCer did not affect c-Jun N-terminal kinase phosphorylation. In conclusion, GlcCer inhibits LPS-induced inflammation by blocking the nuclear translocation of NF-κB and inhibiting the phosphorylation of extracellular signal-regulated kinase/p38 MAPK pathways in macrophages, suggesting that it might be a promising potential drug candidate for various inflammatory diseases.
authors: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea; BK21PLUS Korean Medicine Science Center, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Korea. Electronic address: myeom@khu.ac.kr.
authors: Mijung
authors: M
authors: Yeom
authors: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors: Jinhee
authors: J
authors: Park
authors: Department of Biological Sciences in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors: Changyong
authors: C
authors: Lim
authors: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors: Bongjun
authors: B
authors: Sur
authors: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors: Bombi
authors: B
authors: Lee
authors: Glonet BU, Doosan Corporation, Suwon, 443-270, Korea.
authors: Jeong-Jun
authors: JJ
authors: Han
authors: Korea Food Research Institute, Seongnam, Gyeonggi, 463-746, Republic of Korea.
authors: Hee-Don
authors: HD
authors: Choi
authors: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea; Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors: Hyejung
authors: H
authors: Lee
authors: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea; Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Korea. Electronic address: dhhahm@khu.ac.kr.
authors: Dae-Hyun
authors: DH
authors: Hahm
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005963:Glucosylceramides / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D000067996:RAW 264.7 Cells; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005963:Glucosylceramides; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone
keywords: Inflammation; MAPKs; NF-κB; cyclooxygenase-2; glucosylceramide; macrophage