Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β‐defensin‐1 and ‐2 secretion by colonic epithelial cells. Issue 9 (19th September 2017)

• Record Type: Journal Article
• Authors: Lajczak, Natalia K.; Saint‐Criq, Vinciane; O'Dwyer, Aoife M.; Perino, Alessia; Adorini, Luciano; Schoonjans, Kristina; Keely, Stephen J.
• Is Part Of: FASEB journal. Volume 31:Issue 9(2017)
• Page Start: 3848
• Page End: 3857
• Publication Date: 2017-09-19
• Subjects: HβD -- UDCA -- epithelium -- innate immunity; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201601365R
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: Bile acids and epithelial‐derived human β‐defensins (HβDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HβD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HβD1 and HβD2 from colonic epithelial cells and mucosal tissues. DCA (10–150 μM) stimulated the release of both HβD1 and HβD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro. In contrast, ursodeoxycholic acid (50–200 μM) inhibited both basal and DCA‐induced defensin release. Effects of DCA were mimicked by the Takeda GPCR 5 agonist, INT‐777 (50 μM), but not by the farnesoid X receptor agonist, GW4064 (10 μM). INT‐777 also stimulated colonic HβD1 and HβD2 release from wild‐type, but not Takeda GPCR 5 −/−, mice. DCA stimulated phosphorylation of the p65 subunit of NF‐κB, an effect that was attenuated by ursodeoxycholic acid, whereas an NF‐κB inhibitor, BMS‐345541 (25 μM), inhibited DCA‐induced HβD2, but not HβD1, release. We conclude that bile acids can differentially regulate colonic epithelial HβD 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 β‐defensin‐1 and ‐2 secretion by colonic epithelial cells. FASEB J. 31, 3848–3857 (2017). www.fasebj.org —Lajczak, Natalia K., Saint‐Criq, Vinciane, O'Dwyer, Aoife M., Perino, Alessia, Adorini, Luciano, Schoonjans, Kristina, Keely, Stephen J. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β‐defensin‐1 and ‐2 secretion by colonic epithelial cells. FASEB J. 31, 3848–3857 (2017)