科研之友
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摘要
To investigate the expression of adenosine A3 receptor (A3AR) in human colonic epithelial cells and the effects of A3AR activation on tumor necrosis factor alpha (TNF-alpha-) induced inflammation in order to determine its mechanism of action in human colonic epithelial cells, human colonic epithelial cells (HT-29 cells) were treated with different concentrations of 2-Cl-IB-MECA prior to TNF-alpha stimulation, followed by analysis of NF-kappa B signaling pathway activation and downstream IL-8 and IL-1 beta production. A3AR mRNA and protein were expressed in HT-29 cells and not altered by changes in TNF-alpha or 2-Cl-IB-MECA. Pretreatment with 2Cl-IB-MECA prior to stimulation with TNF-alpha attenuated NF-kappa B p65 nuclear translocation as p65 protein decreased in the nucleus of cells and increased in the cytoplasm, inhibited the degradation of I kappa B-alpha,and reduced phosphorylated-I kappa B-alpha level significantly compared to TNF-alpha-only-treated groups. Furthermore, 2-Cl-IB-MECA significantly decreased TNF-alpha-stimulated IL-8 and IL-1 beta mRNA expression and secretion, compared to the TNF-alpha-only treated group. These results confirm that A3AR is expressed in human colonic epithelial cells and demonstrate that its activation has an anti-inflammatory effect, through the inhibition of NF-kappa B B signaling pathway, which leads to inhibition of downstream IL-8 and IL-1 beta expression. Therefore, A3AR activation may be a potential treatment for gut inflammatory diseases such as inflammatory bowel disease.
- 出版日期2014
- 单位广东医科大学
