Annemarie Boleij, Payam Fathi, William Dalton, Ben Park, Xinqun Wu, David Huso, Jawara Allen, Sepideh Besharati, Robert A Anders, Franck Housseau, Amanda E Mackenzie, Laura Jenkins, Graeme Milligan, Shaoguang Wu, Cynthia L Sears
G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35. Blocking GPR35 function in CECs using the GPR35 antagonist ML145, in conjunction with shRNA knock-down and CRISPRcas-mediated knock-out, resulted in reduced CEC-response to BFT as measured by E-cadherin cleavage, beta-arrestin recruitment and IL-8 secretion...
May 14, 2021: Communications Biology