| First Author | Lajczak NK | Year | 2017 |
| Journal | FASEB J | Volume | 31 |
| Issue | 9 | Pages | 3848-3857 |
| PubMed ID | 28487283 | Mgi Jnum | J:252325 |
| Mgi Id | MGI:5926893 | Doi | 10.1096/fj.201601365R |
| Citation | Lajczak NK, et al. (2017) Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human beta-defensin-1 and -2 secretion by colonic epithelial cells. FASEB J 31(9):3848-3857 |
| abstractText | Bile acids and epithelial-derived human beta-defensins (HbetaDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HbetaD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HbetaD1 and HbetaD2 from colonic epithelial cells and mucosal tissues. DCA (10-150 microM) stimulated the release of both HbetaD1 and HbetaD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro In contrast, ursodeoxycholic acid (50-200 microM) inhibited both basal and DCA-induced defensin release. Effects of DCA were mimicked by the Takeda GPCR 5 agonist, INT-777 (50 muM), but not by the farnesoid X receptor agonist, GW4064 (10 muM). INT-777 also stimulated colonic HbetaD1 and HbetaD2 release from wild-type, but not Takeda GPCR 5-/-, mice. DCA stimulated phosphorylation of the p65 subunit of NF-kappaB, an effect that was attenuated by ursodeoxycholic acid, whereas an NF-kappaB inhibitor, BMS-345541 (25 muM), inhibited DCA-induced HbetaD2, but not HbetaD1, release. We conclude that bile acids can differentially regulate colonic epithelial HbetaD expression and secretion and discuss the implications of our findings for intestinal health and disease.-Lajczak, N. K., Saint-Criq, V., O'Dwyer, A. M., Perino, A., Adorini, L., Schoonjans, K., Keely, S. J. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human beta-defensin-1 and -2 secretion by colonic epithelial cells. |
