RRC ID 19607
Author Noman AS, Koide N, Khuda II, Dagvadorj J, Tumurkhuu G, Naiki Y, Komatsu T, Yoshida T, Yokochi T.
Title Thalidomide inhibits lipopolysaccharide-induced nitric oxide production and prevents lipopolysaccharide-mediated lethality in mice.
Journal FEMS Immunol. Med. Microbiol.
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.
Volume 56(3)
Pages 204-11
Published 2009-8
DOI 10.1111/j.1574-695X.2009.00567.x
PII FIM567
PMID 19538513
MeSH Animals Cell Line Cell Survival Down-Regulation I-kappa B Kinase / metabolism I-kappa B Proteins / metabolism Immunosuppressive Agents / pharmacology* Lipopolysaccharides / immunology* Macrophages / drug effects Macrophages / immunology Mice Mice, Inbred C57BL Myeloid Differentiation Factor 88 / antagonists & inhibitors Nitric Oxide / antagonists & inhibitors* Nitric Oxide Synthase / antagonists & inhibitors Phosphorylation Survival Analysis Thalidomide / pharmacology* Transcription Factor RelA / metabolism
Times Cited 10
WOS Category INFECTIOUS DISEASES MICROBIOLOGY IMMUNOLOGY
Resource
Human and Animal Cells RAW 264 (RCB0535)