title: Glucosamine inhibits lipopolysaccharide-stimulated inducible nitric oxide synthase induction by inhibiting expression of NF-kappaB/Rel proteins at the mRNA and protein levels.
abstract: Expression of inducible nitric oxide synthase (iNOS) protein by lipopolysaccharide (LPS) in BV2 microglia cells increased in a biphasic manner. Glucosamine (GlcN) selectively suppressed the late- but not early-stage iNOS response to LPS. Prolonged induction of iNOS expression by LPS was inhibited by cycloheximide, suggesting that de novo protein synthesis was required. Late-phase activation of nuclear factor-kappaB (NF-κB) activity required for sustained iNOS induction. Nuclear translocation and DNA binding of NF-κB, and Rel proteins expressions were inhibited by GlcN at later time points but not upon immediate early-stage activation by LPS. We show that GlcN selectively inhibits sustained iNOS induction by inhibiting Rel protein expression at both the mRNA and protein levels; such expression is required for prolonged iNOS induction by LPS. Our results provide mechanistic evidence that GlcN regulates inflammation, represented by iNOS. The implication of these results is that GlcN may be a potent transcriptional regulator of iNOS and other genes involved in the general inflammation process.
authors: Department of Physiology and Biophysics, Inha University, College of Medicine, Incheon, Republic of Korea.
authors: So-Young
authors: SY
authors: Hwang
authors: Ji-Sun
authors: JS
authors: Hwang
authors: Song-Yi
authors: SY
authors: Kim
authors: Inn-Oc
authors: IO
authors: Han
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects; D005944:Glucosamine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000378:metabolism; D020572:Oncogene Proteins v-rel / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D020572:Oncogene Proteins v-rel; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D005944:Glucosamine