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

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-kappa B 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 kappa B-driven luciferase expression and a reduction in recruitment of NF-kappa B 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. (c) 2005 Elsevier Inc. All rights reserved.