title: Activation of adenosine A3 receptor alleviates TNF-α-induced inflammation through inhibition of the NF-κB signaling pathway in human colonic epithelial cells.
abstract: 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-α-) 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-α stimulation, followed by analysis of NF-κB signaling pathway activation and downstream IL-8 and IL-1β production. A3AR mRNA and protein were expressed in HT-29 cells and not altered by changes in TNF-α or 2-Cl-IB-MECA. Pretreatment with 2-Cl-IB-MECA prior to stimulation with TNF-α attenuated NF-κB p65 nuclear translocation as p65 protein decreased in the nucleus of cells and increased in the cytoplasm, inhibited the degradation of IκB-α, and reduced phosphorylated-IκB-α level significantly, compared to TNF-α-only-treated groups. Furthermore, 2-Cl-IB-MECA significantly decreased TNF-α-stimulated IL-8 and IL-1β mRNA expression and secretion, compared to the TNF-α-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-κB signaling pathway, which leads to inhibition of downstream IL-8 and IL-1β expression. Therefore, A3AR activation may be a potential treatment for gut inflammatory diseases such as inflammatory bowel disease.
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Ren
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Shicai
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Caiyuan
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D003106:Colon / Q000166:cytology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D053583:Interleukin-1beta; D016209:Interleukin-8; D016328:NF-kappa B; D043684:Receptor, Adenosine A3; D014409:Tumor Necrosis Factor-alpha; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide