P014 Proinflammatory cytokines and bile salts inhibit the cellular uptake of butyrate by Caco-2 cells. (16th January 2018)

• Record Type: Journal Article
• Authors: Couto, M; Andrade, N; Correia-Branco, A; Magro, F; Martel, F
• Is Part Of: Journal of Crohn's and colitis. Volume 12:Number 1(2018:Jan.)Supplement 1
• Page Start: S098
• Page End: S100
• Publication Date: 2018-01-16
• Subjects: Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjx180.141
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: Butyrate (BT) is a short-chain fatty acid produced in the intestinal lumen by bacterial fermentation of undigested dietary fibre. Besides being the main energy source for colonic epithelium, BT also stimulates proliferation and differentiation of healthy colonocytes, induces apoptosis of transformed cells and has anti-inflammatory properties. BT has been implicated in inflammatory bowel disease (IBD) pathogenesis and as adjuvant treatment (Nolan et al. 2013). Our group recently demonstrated that BT uptake by intestinal epithelial cells is inhibited by the primary bile salt chenodeoxycholic acid (Gonçalves et al. 2012). Because bile salt malabsorption, resulting in higher luminal concentrations of bile salts, is a common sign of IBD (Nolan et al. 2013), we decided to investigate the hypothesis that a negative interaction of bile salts and BT, mediated by bile salt-mediated inhibition of BT intestinal epithelial uptake, contributes to the etiopathogenesis of IBD. Methods: We characterised uptake of 14C-BT in an intestinal epithelial cell line (Caco-2) in the presence of pro-inflammatory cytokines (TNF-α e IFN-γ) and/or some bile salts, including CDCA and deoxycholic acid (DCA). Results: TNF-α and IFN-γ time- and concentration-dependently inhibited 14C-BT uptake; uptake of 14C-BT was reduced to about 50% after exposure to 100 ng/ml TNF-α or IFN-γ for 24h. CDCA and CDA (300 µM; 24h) also inhibit 14C-BT uptake (to 20 and 30% of control, respectively). The inhibitory effect of these compounds upon 14C-BT uptake does not result from a cytotoxic effect. Uptake of 14C-BT by Caco-2 cells is not affected by Na+ omission, which is compatible with H(+)-coupled monocarboxylate transporter 1 (MCT1) involvement. TNF-α, IFN-γ, CDCA and DCA appear to inhibit MCT1-mediated 14C-BT uptake, as their effect is similar in the presence or absence of Na + and is not affected by the presence of an MCT1 inhibitor. Moreover, the inhibitory effect of the CDCA and CDA on 14C-BT uptake is not affected by the presence of proinflammatory cytokines. Conclusions: In Caco-2 cells, 14C-BT uptake seems to be mediated by MCT1. TNF-α, IFN-γ, CDCA and DCA appear to inhibit MCT1-mediated 14C-BT uptake, but their effect is not additive. Given the anti-inflammatory effect of BT, this effect of proinflammatory cytokines and bile salts, present in higher amounts in IBD, might contribute to the ethiopathogenesis of IBD.