The effects of thalidomide on the stimulation of NF-kappaB activity and TNF-alpha production by lipopolysaccharide in a human colonic epithelial cell line

Mol Cells. 2004 Apr 30;17(2):210-6.


The immunomodulatory and anti-inflammatory effects of thalidomide are associated with inhibition of TNF-alpha levels. However, the mechanism by which thalidomide reduces TNF-alpha production remains elusive. NF-kappaB is known to play a central role in regulating inflammatory responses in patients with inflammatory bowel disease (IBD). We tested whether thalidomide acts through inhibiting NF-kappaB activity. HT-29 cells were stimulated with LPS (1 microg/ml) alone, or after pretreatment with thalidomide (100 microg/ml), and NF-kappaB activity was determined by gel mobility shift assays. RT-PCR was used to measure expression of the proinflammatory cytokine genes TNF-alpha, IL-1beta and IL-8. The level of TNF-alpha mRNA was also analyzed by real-time quantitative RT-PCR, and TNF-alpha protein was measured by ELISA. Thalidomide pretreatment did not affect NF-kappaB activity in HT-29 cells stimulated with LPS but production of TNF-alpha was depressed. Thalidomide was found to accelerate the degradation of TNF-alpha mRNA, but had little effect on IL-1beta or IL-8. These observations suggest that the immunomodulatory effect of thalidomide in colonic epithelial cells is associated with inhibition of TNF-alpha. However, it does not act by inhibiting NF-kappaB but rather by inducing degradation of TNF-alpha mRNA.

MeSH terms

  • Cell Line
  • Colon / anatomy & histology*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Lipopolysaccharides / pharmacology*
  • NF-kappa B / metabolism*
  • RNA, Messenger / metabolism
  • Thalidomide / pharmacology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*


  • Immunosuppressive Agents
  • Interleukin-1
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Thalidomide