Clinicalresearch
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 28, 2007; 13(20): 2826-2832
Published online May 28, 2007. doi: 10.3748/wjg.v13.i20.2826
Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: A study with relevance to inflammatory bowel disease
Sofia Tedelind, Fredrik Westberg, Martin Kjerrulf, Alexander Vidal
Sofia Tedelind, Fredrik Westberg, Martin Kjerrulf, Alexander Vidal, Department of Molecular Pharmacology, AstraZeneca R&D, Mölndal, Sweden
Author contributions: All authors contributed equally to the work.
Correspondence to: Alexander Vidal, PhD, Department of Molecular Pharmacology, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden. alexander.vidal@astrazeneca.com
Telephone: +46-31-7762926 Fax: +46-31-7763761
Received: February 9, 2007
Revised: March 3, 2007
Accepted: March 15, 2007
Published online: May 28, 2007
Abstract

AIM: To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation.

METHODS: The effect of SCFAs on cytokine release from human neutrophils was studied with ELISA. SCFA-dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice.

RESULTS: Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures.

CONCLUSION: In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.

Keywords: Neutrophils; Epithelial cells; Colitis; Infla-mmation; Short-chain fatty acids; Acetate; Propionate; Butyrate; NF-κB; Cytokines