UII/GPR14 is involved in NF-κB-mediated colonic inflammation in vivo and in vitro.

Abstract

The present study was conducted to investigate the molecular mechanism of urotensinII (UII) and its receptor, Gprotein‑coupled receptor 14 (GPR14), in colonic inflammation. Urantide, a special antagonist of GPR14, and GPR14-siRNA were used to inhibit GPR14 signaling in dextran sulfate sodium (DSS)‑induced inflammation in mice and Caco-2 cells. The results showed that urantide alleviated rectal bleeding, histological injury and production of interleukin (IL)-17 and tumor necrosis factor‑α (TNF‑α) caused by DSS in mice. GPR14-siRNA transfection subsequent with GPR14 inhibition reduced DSS-induced interferon-γ (IFN)-γ production in Caco-2 cells. Meanwhile, both invivo and invitro data demonstrated that inhibition of UII/GPR14 alleviated nuclear factor-κB (NF-κB) activation caused by DSS. In conclusion, UII/GPR14 signaling was involved in the DSS-induced colonic inflammation and its inhibition may serve as a potential therapeutic target, which may be associated with the NF-κB signaling pathway.