Open AccessThalidomide inhibits lipopolysaccharide‐induced nitric oxide production and prevents lipopolysaccharide‐mediated lethality in mice
Author(s) -
Noman Abu Shadat M.,
Koide Naoki,
Khuda Imtiaz I.E.,
Dagvadorj Jargalsaikhan,
Tumurkhuu Gantsetseg,
Naiki Yoshikazu,
Komatsu Takayuki,
Yoshida Tomoaki,
Yokochi Takashi
Publication year - 2009
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2009.00567.x
Subject(s) - lipopolysaccharide , lethality , nitric oxide , thalidomide , biology , pharmacology , microbiology and biotechnology , ratón , immunology , endocrinology , toxicology , multiple myeloma
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‐κB subunit, inhibitory κB (IκB) and IκB kinase in lipopolysaccharide‐stimulated cells. However, thalidomide did not affect the expression of interferon‐β (IFN‐β) 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‐β 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.