G protein coupled receptor 18 activation during experimental colitis in mice

Area of Science:

• Gastroenterology
• Immunology
• Pharmacology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with increasing prevalence.
• Current treatments for UC do not achieve complete remission, necessitating novel therapeutic strategies.
• G protein coupled receptor 18 (GPR18) is a potential target for modulating intestinal inflammation.

Purpose of the Study:

• To evaluate the therapeutic potential of PSB-KK-1415, a GPR18 receptor agonist, in a mouse model of intestinal inflammation.
• To assess the impact of PSB-KK-1415 on human epithelial cell viability.
• To investigate the expression of GPR18 during different stages of colitis.

Main Methods:

• PSB-KK-1415's effect on CCD 841 CON cell viability was assessed using MTT assay.
• Dextran sodium sulfate (DSS) was used to induce acute and chronic colitis in mice.
• GPR18 mRNA expression was quantified using real-time RT-PCR; anti-inflammatory effects were evaluated macroscopically and microscopically.

Main Results:

• PSB-KK-1415 did not affect epithelial cell viability.
• GPR18 mRNA expression was upregulated in early/moderate colitis and downregulated in severe colitis/recovery.
• PSB-KK-1415 treatment reduced colonic inflammation, improved intestinal wall thickness, and decreased MPO activity in DSS-induced colitis models.

Conclusions:

• Activation of the GPR18 receptor shows promise for treating intestinal inflammation.
• PSB-KK-1415 demonstrates anti-inflammatory properties in mouse models of UC.
• Targeting GPR18 may be a viable strategy for managing chronic colitis.