Adenosine is a negative regulator of NF-kappaB and MAPK signaling in human intestinal epithelial cells

Cell Immunol. 2005 Oct;237(2):86-95. doi: 10.1016/j.cellimm.2005.10.005.


Previous studies suggest that adenosine possesses anti-inflammatory properties, however, the mechanisms by which adenosine affects immune function remain unclear, particularly in the intestine. In this study, we hypothesized that adenosine directly affects pro-inflammatory gene expression in intestinal epithelial cells through modulation of NF-kappaB signaling. HT-29 cells were treated with adenosine prior to incubation with various stimuli and pro-inflammatory gene expression and signal transduction analyzed. Adenosine pretreatment resulted in a reduction in IL-8 expression and secretion in response to TNF-alpha, IL-1, LPS, and PMA. This effect was paralleled by inhibition of kappaB-driven luciferase expression and a reduction in recruitment of NF-kappaB to the IL-8 promoter. Pretreatment of HT-29 cells also resulted in reduced ERK, p38, and JNK MAPK phosphorylation, following TNF-alpha treatment. The observed effects in this study occurred independently of known surface adenosine receptors. This study identifies adenosine as a potent negative regulator of pro-inflammatory signaling in intestinal epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / pharmacology*
  • Anti-Inflammatory Agents / pharmacology
  • Base Sequence
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Gene Expression / drug effects
  • Genes, Reporter / drug effects
  • HT29 Cells
  • Humans
  • Interleukin-1 / pharmacology
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects*
  • Intestines / immunology
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System / drug effects*
  • NF-kappa B / metabolism*
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Purinergic P1 / metabolism
  • Signal Transduction / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology


  • Anti-Inflammatory Agents
  • Interleukin-1
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Purinergic P1
  • Tumor Necrosis Factor-alpha
  • Adenosine
  • Tetradecanoylphorbol Acetate