title: Inhibitory effects of short-chain fatty acids on matrix metalloproteinase secretion from human colonic subepithelial myofibroblasts.
abstract: OBJECTIVE
  Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are the major by-product of bacterial fermentation of dietary fiber in the colon. In this report, we investigated how SCFAs modulate matrix metalloproteinase (MMP) secretion from human colonic subepithelial myofibroblasts (SEMFs).
  
  
  METHODS
  SEMFs were identified by expression of alpha-smooth muscle actin and vimentin. Cytokine-induced MMP-1 and MMP-3 levels were determined by enzyme-linked immunosorbent assay. Cytokine-induced MMP mRNA expression was analyzed by RT-PCR and real-time PCR methods.
  
  
  RESULTS
  Acetate had no effect on MMP secretion. Propionate and butyrate significantly attenuated IL-1 beta- and TNF-alpha-induced MMP-1 and MMP-3 secretion. Similar responses were also observed at the mRNA levels. Propionate and butyrate did not modulate IL-1 beta- and TNF-alpha-induced activation of mitogen-activated protein kinases (MAPKs), which play a crucial role in MMP induction. Trichostatin A, a histone-deacetylase inhibitor, reduced IL-1 beta-induced MMP-1 and MMP-3 mRNA expression, and suppressed TNF-alpha-induced MMP-3 mRNA expression.
  
  
  CONCLUSIONS
  SCFAs play an anti-inflammatory role through suppression of MMP secretion in the colon. Inhibitory effects of SCFAs on MMP secretion might be associated with their action of histone hyperacetylation.
authors.affiliation: Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu, 520-2192, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Kawamura
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
authors.forename: Makoto
authors.initials: M
authors.lastname: Shioya
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Yagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tsujikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
mesh_terms: D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D005232:Fatty Acids, Volatile / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids; D053583:Interleukin-1beta / Q000502:physiology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D005232:Fatty Acids, Volatile; D006877:Hydroxamic Acids; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C012589:trichostatin A; D020928:Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1