Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human ß-defensin-1 and -2 secretion by colonic epithelial cells.
FASEB J
; 31(9): 3848-3857, 2017 09.
Article
in En
| MEDLINE
| ID: mdl-28487283
ABSTRACT
Bile acids and epithelial-derived human ß-defensins (HßDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HßD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HßD1 and HßD2 from colonic epithelial cells and mucosal tissues. DCA (10-150 µM) stimulated the release of both HßD1 and HßD2 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 HßD1 and HßD2 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 HßD2, but not HßD1, release. We conclude that bile acids can differentially regulate colonic epithelial HßD 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 ß-defensin-1 and -2 secretion by colonic epithelial cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ursodeoxycholic Acid
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Colon
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Beta-Defensins
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Deoxycholic Acid
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Intestinal Mucosa
Limits:
Animals
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Humans
Language:
En
Journal:
FASEB J
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2017
Document type:
Article
Affiliation country: