Digestive Diseases and Sciences

, Volume 52, Issue 11, pp 2963–2971 | Cite as

Clostridium butyricum TO-A Culture Supernatant Downregulates TLR4 in Human Colonic Epithelial Cells

  • Atsushi Isono
  • Tatsuro Katsuno
  • Toru Sato
  • Tomoo Nakagawa
  • Yasutaka Kato
  • Naoki Sato
  • Gen’ichiro Seo
  • Yasuo Suzuki
  • Yasushi Saito
Original Paper


The present study was performed to examine whether probiotics affect Toll-like receptor 4 (TLR4) expression in human colonic epithelial cells. Culture supernatants or heat-killed bacteria of Bacillus mesentericus TO-A, Clostridium butyricum TO-A, and Streptococcus faecalis T-110 were applied to human colonic epithelial cells. Treatment with C. butyricum TO-A culture supernatant significantly reduced TLR4 mRNA level (×0.16), even in the presence of interferon-γ (IFN-γ; ×0.21) as compared with untreated controls. High-performance liquid chromatography analysis showed that C. butyricum TO-A supernatant contains formate, acetate, and butyrate. Interestingly, TLR4 mRNA was significantly suppressed (×0.15–×0.22) only when cells were treated with solutions containing butyrate. Electrophoretic mobility shift assay suggested that the binding affinity of PU.1 to the promoter region of the TLR4 gene was markedly inhibited when the cells were treated with butyrate. This study suggested that butyrate produced by C. butyricum TO-A downregulates TLR4 mRNA level in human colonic epithelial cells.


Toll-like receptor 4 HT-29 human colonic epithelial cells Clostridium butyricum TO-A Butyrate PU.1 


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Atsushi Isono
    • 1
  • Tatsuro Katsuno
    • 1
  • Toru Sato
    • 1
  • Tomoo Nakagawa
    • 1
  • Yasutaka Kato
    • 1
  • Naoki Sato
    • 2
  • Gen’ichiro Seo
    • 2
  • Yasuo Suzuki
    • 3
  • Yasushi Saito
    • 1
  1. 1.Department of Clinical Cell Biology (F5)Graduate School of Medicine, Chiba UniversityChibaJapan
  2. 2.Toa Pharmaceutical Co., Ltd.TatebayashiJapan
  3. 3.Department of Internal MedicineToho University Sakura Medical CenterChibaJapan

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