Thalidomide inhibits lipopolysaccharide-induced tumor necrosis factor-α production via down-regulation of MyD88 expression

Abu Shadat M. Noman, Naoki Koide, Ferdaus Hassan, Imtiaz I.-E-Khuda, Jargalsaikhan Dagvadorj, Gantsetseg Tumurkhuu, Shamima Islam, Yoshikazu Naiki, Tomoaki Yoshida, Takashi Yokochi

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

The effect of thalidomide on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production was studied by using RAW 264.7 murine macrophage-like cells. Thalidomide significantly inhibited LPS-induced TNF-α production. Thalidomide prevented the activation of nuclear factor (NF)-KB by down-regulating phosphorylation of inhibitory KB factor (IKB), and IKB kinase (IKK)-α and IKK-β Moreover, thalidomide inhibited LPS-induced phosphorylation of AKT, p38 and stress-activated protein kinase (SAPK)/JNK. The expression of myeloid differentiation factor 88 (MyD88) protein and mRNA was markedly reduced in thalidomide-treated RAW 264.7 cells but there was no significant alteration in the expression of interleukin-1 receptor-associated kinase (IRAK) 1 and TNF receptor-associated factor (TRAF) 6 in the cells. Thalidomide did not affect the cell surface expression of Toll-like receptor (TLR) 4 and CD14, suggesting the impairment of intracellular LPS signalling in thalidomide-treated RAW 264.7 cells. Thalidomide significantly inhibited the TNF-α production in response to palmitoyl-Cys(RS)-2,3-di(palmitoyloxy) propyl)-Ala-Gly-OH (Pam3Cys) as a MyD88-dependent TLR2 ligand. Therefore, it is suggested that thalidomide might impair LPS signalling via down-regulation of MyD88 protein and mRNA and inhibit LPS-induced TNF-α production. The putative mechanism of thalidomide-induced MyD88 down-regulation is discussed.

Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalInnate Immunity
Volume15
Issue number1
DOIs
Publication statusPublished - 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Thalidomide inhibits lipopolysaccharide-induced tumor necrosis factor-α production via down-regulation of MyD88 expression'. Together they form a unique fingerprint.

Cite this