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

Area of Science:

• Gastroenterology
• Molecular Biology
• Immunology

Background:

• Colonic inflammation is a significant health concern.
• Urotensin II (UII) and its receptor G-protein-coupled receptor 14 (GPR14) signaling pathways are implicated in inflammatory processes.
• Understanding the precise role of UII/GPR14 in colonic inflammation is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the molecular mechanism of urotensin II (UII) and its receptor, G-protein-coupled receptor 14 (GPR14), in dextran sulfate sodium (DSS)-induced colonic inflammation.
• To evaluate the therapeutic potential of inhibiting the UII/GPR14 pathway in colonic inflammation.

Main Methods:

• Utilized a dextran sulfate sodium (DSS)-induced mouse model of colonic inflammation.
• Employed GPR14 inhibition using urantide (antagonist) and GPR14-siRNA in both in vivo (mice) and in vitro (Caco-2 cells) settings.
• Assessed key inflammatory markers including rectal bleeding, histological injury, and cytokine production (IL-17, TNF-α, IFN-γ).
• Investigated the impact on nuclear factor-kappa B (NF-κB) activation.

Main Results:

• Urantide treatment significantly alleviated DSS-induced rectal bleeding, histological damage, and the production of IL-17 and TNF-α in mice.
• GPR14 inhibition via siRNA transfection reduced DSS-induced IFN-γ production in Caco-2 cells.
• Both in vivo and in vitro studies demonstrated that inhibiting UII/GPR14 signaling attenuated DSS-induced NF-κB activation.

Conclusions:

• The UII/GPR14 signaling pathway plays a significant role in DSS-induced colonic inflammation.
• Inhibition of UII/GPR14 signaling demonstrates potential as a therapeutic strategy for colonic inflammation.
• The anti-inflammatory effects are potentially mediated through the modulation of the NF-κB signaling pathway.