title: Thalidomide inhibits lipopolysaccharide-induced nitric oxide production and prevents lipopolysaccharide-mediated lethality in mice.
abstract: The effect of thalidomide on lipopolysaccharide-induced nitric oxide (NO) production was studied using RAW 264.7 macrophage-like cells. Thalidomide significantly inhibited lipopolysaccharide-induced NO production via reduced expression of an inducible NO synthase. Thalidomide reduced the phosphorylation of the p65 nuclear factor-kappaB subunit, inhibitory kappaB (IkappaB) and IkappaB kinase in lipopolysaccharide-stimulated cells. However, thalidomide did not affect the expression of interferon-beta (IFN-beta) and interferon regulatory factor-1 in response to lipopolysaccharide. Further, thalidomide inhibited the MyD88 augmentation in lipopolysaccharide-stimulated cells, whereas it did not alter the expression of TIR domain-containing adaptor-inducing IFN-beta in the MyD88-independent pathway. Thalidomide significantly inhibited the NO production in response to Pam(3)Cys, CpG DNA and imiquimod as MyD88-dependent Toll-like receptor (TLR) ligands, but not polyI:C as a MyD88-independent TLR ligand. Therefore, thalidomide was suggested to inhibit lipopolysaccharide-induced NO production via downregulation of the MyD88-dependent signal pathway. The anti-inflammatory action of thalidomide might be involved in the prevention of lipopolysaccharide-mediated lethality in mice.
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Aichi 480-1195, Japan.
authors.forename: Abu Shadat M
authors.initials: AS
authors.lastname: Noman
authors.forename: Naoki
authors.initials: N
authors.lastname: Koide
authors.forename: Imtiaz I-E
authors.initials: II
authors.lastname: Khuda
authors.forename: Jargalsaikhan
authors.initials: J
authors.lastname: Dagvadorj
authors.forename: Gantsetseg
authors.initials: G
authors.lastname: Tumurkhuu
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Naiki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Komatsu
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D015536:Down-Regulation; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D016019:Survival Analysis; D013792:Thalidomide / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051996:Transcription Factor RelA; D009569:Nitric Oxide; D013792:Thalidomide; D019001:Nitric Oxide Synthase; D051550:I-kappa B Kinase