UII/GPR14 is involved in NF-κB-mediated colonic inflammation in vivo and in vitro.
The present study was conducted to investigate the molecular mechanism of urotensin II (UII) and its receptor, G protein‑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 in vivo and in vitro 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.
Department of General Surgery, Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Yi
Y
Yang
Department of Encephalopathy, Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712000, P.R. China.
Jinpei
J
Zhang
Department of General Surgery, Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Xi
X
Chen
Department of General Surgery, Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Tao
T
Wu
Department of General Surgery, Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Xin
X
Xu
Department of General Surgery, Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Gang
G
Cao
Department of General Surgery, Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Hua
H
Li
Department of General Surgery, Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Yiming
Y
Li
D000818:Animals; D018938:Caco-2 Cells; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D006470:Hemorrhage / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics*; D012007:Rectum / Q000473:pathology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014579:Urotensins / Q000096:biosynthesis / Q000235:genetics*
D020381:Interleukin-17; D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C121697:UTS2R protein, human; D014579:Urotensins; D016264:Dextran Sulfate; C029677:urotensin II