title: Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease.
abstract: OBJECTIVE
  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-kappaB 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 TNFalpha release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-kappaB 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.
  
  
  CONCLUSIONS
  In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-kappaB 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.
authors.affiliation: Department of Molecular Pharmacology, AstraZeneca R&D Molndal, SE-431 83 Molndal, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Tedelind
authors.forename: Fredrik
authors.initials: F
authors.lastname: Westberg
authors.forename: Martin
authors.initials: M
authors.lastname: Kjerrulf
authors.forename: Alexander
authors.initials: A
authors.lastname: Vidal
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000085:Acetates; D000893:Anti-Inflammatory Agents; D002087:Butyrates; D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D011422:Propionates; D014409:Tumor Necrosis Factor-alpha