Abstract
The role of the adenosine A3 receptor (A3AR) in experimental colitis is controversial. The A3AR agonist N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) has been shown to have a clinical benefit, although studies in A3AR-deficient mice suggest a pro-inflammatory role. However, there are no studies on the effect of 2-Cl-IB-MECA and the molecular mechanism of action of A3AR in murine colitis models in vivo. Is it the same as that observed in vitro? The interaction between 2-CL-IB-MECA and A3AR in a murine colitis model and the signaling pathways associated with this interaction remain unclear. Here we demonstrate a role for the NF-κB signaling pathway and its effect on modifying the activity of proinflammatory factors in A3AR-mediated biological processes. Our results demonstrated that A3AR activation possessed marked effects on experimental colitis through the NF-κB signaling pathway.
Highlights
An adenosine A3 receptor agonist inhibits Dextran sulfate sodium (DSS)-induced colitis in mice through modulation of the Nuclear factor-kappa B (NF-kB) signaling pathway
There are no studies on the effect of 2-Cl-IB-MECA and the molecular mechanism of action of A3AR in murine colitis models in vivo
Is it the same as that observed in vitro? The interaction between 2-CL-IB-MECA and A3AR in a murine colitis model and the signaling pathways associated with this interaction remain unclear
Summary
An adenosine A3 receptor agonist inhibits DSS-induced colitis in mice through modulation of the NF-kB signaling pathway. The A3AR agonist N6-(3-iodobenzyl)adenosine-5’-N-methyluronamide (IB-MECA) has been shown to have a clinical benefit, studies in A3AR-deficient mice suggest a pro-inflammatory role. The interaction between 2-CL-IB-MECA and A3AR in a murine colitis model and the signaling pathways associated with this interaction remain unclear. We demonstrate a role for the NF-kB signaling pathway and its effect on modifying the activity of proinflammatory factors in A3AR-mediated biological processes. Our results demonstrated that A3AR activation possessed marked effects on experimental colitis through the NF-kB signaling pathway. The chronic mucosal inflammation in IBD is caused by hyperactivation of effector immune cells, which produce high levels of pro-inflammatory cytokines like tumor necrosis factoralpha (TNF-a), interleukin-1beta (IL-1b), and interferon-gamma (IFN-c), thereby resulting in colonic tissue damage. Colitis may result from DSS toxicity to colonic epithelial cells
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