Activation of adenosine A3 receptor inhibits inflammatory cytokine production in colonic mucosa of patients with ulcerative colitis by down-regulating the nuclear factor-kappa B signaling.

Abstract

The activation of the adenosine A3 receptor (A3AR) can regulate inflammation, but the way that this regulates colonic mucosal inflammation in ulcerative colitis (UC) remains unclear. This study aimed at examining A3AR expression and investigating the effect of A3AR activation on ex vivo cytokine expression and nuclear factor-kappa B (NF-κB) signaling in colonic mucosa. Colonic mucosal biopsied tissue from 18 patients with UC and 11 healthy controls was tested for A3AR expression by immunofluorescence, quantitative real-time polymerase chain reaction and Western blot. Following treatment for 24 hours with or without 2-Cl-IB-MECA, an A3AR agonist, TNF-α and IL-1β secreted by the cultured colonic mucosal tissue were quantified by ELISA. The colonic mucosal epithelia were dissected and treated with, or without 2-Cl-IB-MECA for 24 hours. The NF-κB p65 protein and its distribution in the cultured colonic epithelia were examined by immunofluorescence and Western blot. Compared with the controls, down-regulated A3AR expression and up-regulated TNF-α and IL-1β production and NF-κB p65 protein were observed in the UC colonic mucosa. The activation of A3AR by 2-Cl-IB-MECA significantly decreased TNF-α and IL-1β production and attenuated the NF-κB p65 activation in colonic tissues from patients with UC. A3AR activation inhibited inflammation by mitigating pro-inflammatory cytokine production and the NF-κB signal activation in colonic mucosa of patients with UC. A3AR activation may play a role in the pathogenesis of UC.