Inhibitory Effects of Short-Chain Fatty Acids on Matrix Metalloproteinase Secretion from Human Colonic Subepithelial Myofibroblasts

  • Takato Kawamura
  • Akira Andoh
  • Atsushi Nishida
  • Makoto Shioya
  • Yuhki Yagi
  • Takashi Nishimura
  • Takayoshi Hashimoto
  • Tomoyuki Tsujikawa
  • Hiroyuki Yasui
  • Yoshihide Fujiyama
Original Article

Abstract

Background and Aims 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). Materials and Methods SEMFs were identified by expression of α-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-1β- and TNF-α-induced MMP-1 and MMP-3 secretion. Similar responses were also observed at the mRNA levels. Propionate and butyrate did not modulate IL-1β- and TNF-α-induced activation of mitogen-activated protein kinases (MAPKs), which play a crucial role in MMP induction. Trichostatin A, a histone-deacetylase inhibitor, reduced IL-1β-induced MMP-1 and MMP-3 mRNA expression, and suppressed TNF-α-induced MMP-3 mRNA expression. Conclusion 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.

Keywords

Trichostatin A Histone acetylation TNF-α 

Abbreviations

IL

Interleukin

TNF

Tumor necrosis factor

DMEM

Dulbecco’s modified Eagle’s medium

ELISA

Enzyme-linked immunosorbent assay

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Takato Kawamura
    • 1
    • 2
  • Akira Andoh
    • 1
  • Atsushi Nishida
    • 1
  • Makoto Shioya
    • 1
  • Yuhki Yagi
    • 1
  • Takashi Nishimura
    • 1
  • Takayoshi Hashimoto
    • 1
  • Tomoyuki Tsujikawa
    • 1
  • Hiroyuki Yasui
    • 2
  • Yoshihide Fujiyama
    • 1
  1. 1.Department of Internal MedicineShiga University of Medical ScienceSeta-TukinowaJapan
  2. 2.Department of Analytical and Bioinorganic ChemistryKyoto Pharmaceutical UniversityKyotoJapan

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