Digestive Diseases and Sciences

, Volume 54, Issue 2, pp 255–263 | Cite as

The Effect of Saccharomyces boulardii on Human Colon Cells and Inflammation in Rats with Trinitrobenzene Sulfonic Acid-Induced Colitis

Original Article

Abstract

Saccharomyces boulardii (S. boulardii) has beneficial effects in the treatment of intestinal inflammation; however, little is known about the mechanisms by which these effects occur. We investigated the effects of S. boulardii on the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and interleukin-8 (IL-8), using human HT-29 colonocytes and a rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. The effect of S. boulardii on gene expression was assessed by semi-quantitative reverse transcription–polymerase chain reaction (RT-PCR), and Northern blot and Western blot assays. Pharmacological inhibitors for various signaling pathways were used to determine the signaling pathways implicated in the S. boulardii regulation of PPAR-γ and IL-8. We found that S. boulardii up-regulated and down-regulated PPAR-γ and IL-8 expression at the transcription level, both in vitro and in vivo (P < 0.05, respectively). Saccharomyces boulardii blocked tumor necrosis factor-alpha (TNF-α) regulation of PPAR-γ and IL-8 through disruption of TNF-α-mediated nuclear factor kappa B (NF-κB) activation. Furthermore, S. boulardii suppressed colitis and expression of pro-inflammatory cytokine genes in vivo (P < 0.05, respectively). Our study demonstrated that S. boulardii reduces colonic inflammation and regulates inflammatory gene expression.

Keywords

Saccharomyces boulardii PPAR-γ IL-8 HT-29 TNBS-induced colitis 

References

  1. 1.
    Podolsky DK (1991) Inflammatory bowel disease. N Engl J Med 325:928–937PubMedGoogle Scholar
  2. 2.
    Podolsky DK (1991) Inflammatory bowel disease. N Engl J Med 325:1008–1016PubMedGoogle Scholar
  3. 3.
    Hanauer SB (1996) Inflammatory bowel disease. N Engl J Med 334:841–848. doi:10.1056/NEJM199603283341307 PubMedCrossRefGoogle Scholar
  4. 4.
    Fuller R (1989) Probiotics in man and animals. J Appl Bacteriol 66:365–378PubMedGoogle Scholar
  5. 5.
    Goossens D, Jonkers D, Stobberingh E, van den Bogaard A, Russel M, Stockbrugger R (2003) Probiotics in gastroenterology: indications and future perspectives. Scand J Gastroenterol 239:15–23Google Scholar
  6. 6.
    Plein K, Hotz J (1993) Therapeutic effects of Saccharomyces boulardii on mild residual symptoms in a stable phase of Crohn’s disease with special respect to chronic diarrhea—a pilot study. Z Gastroenterol 31:129–134PubMedGoogle Scholar
  7. 7.
    Guslandi M, Mezzi G, Sorghi M, Testoni PA (2000) Saccharomyces boulardii in maintenance treatment of Crohn’s disease. Dig Dis Sci 45:1462–1464. doi:10.1023/A:1005588911207 PubMedCrossRefGoogle Scholar
  8. 8.
    Neish AS, Gewirtz AT, Zeng H, Young AN, Hobert ME, Karmali V et al (2000) Prokaryotic regulation of epithelial responses by inhibition of IkB-α ubiquitination. Science 289:1560–1563. doi:10.1126/science.289.5484.1560 PubMedCrossRefGoogle Scholar
  9. 9.
    Sougioultzis S, Simeonidis S, Bhaskar KRB, Chen X, Anton PM, Keates S et al (2006) Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-kB-mediated IL-8 gene expression. Biochem Biophys Res Commun 343:69–76. doi:10.1016/j.bbrc.2006.02.080 PubMedCrossRefGoogle Scholar
  10. 10.
    Schoonjans K, Staels B, Auwerx J (1996) Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 37:907–925PubMedGoogle Scholar
  11. 11.
    Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM (1994) mPPARγ2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 8:1224–1234. doi:10.1101/gad.8.10.1224 PubMedCrossRefGoogle Scholar
  12. 12.
    Strober W, Fuss IJ, Blumberg RS (2002) The immunology of mucosal models of inflammation. Annu Rev Immunol 20:495–549. doi:10.1146/annurev.immunol.20.100301.064816 PubMedCrossRefGoogle Scholar
  13. 13.
    Di Sabatino A, Ciccocioppo R, Luinetti O, Ricevuti L, Morera R, Cifone MG et al (2003) Increased enterocyte apoptosis in inflamed areas of Crohn’s disease. Dis Colon Rectum 46:1498–1507. doi:10.1007/s10350-004-6802-z PubMedCrossRefGoogle Scholar
  14. 14.
    Jones DC, Ding X, Daynes RA (2002) Nuclear receptor peroxisome proliferator-activated receptor α (PPARα) is expressed in resting murine lymphocytes. The PPAR alpha in T and B lymphocytes is both transactivation and transrepression competent. J Biol Chem 277:6838–6845. doi:10.1074/jbc.M106908200 PubMedCrossRefGoogle Scholar
  15. 15.
    Cunard R, DiCampli D, Archer DC, Stevenson JL, Ricote M, Glass CK et al (2002) WY14, 643, a PPAR α ligand, has profound effects on immune responses in vivo. J Immunol 169:6806–6812PubMedGoogle Scholar
  16. 16.
    Wang YL, Frauwirth KA, Rangwala SM, Lazar MA, Thompson CB (2002) Thiazolidinedione activation of peroxisome proliferator-activated receptor γ can enhance mitochondrial potential and promote cell survival. J Biol Chem 277:31781–31788. doi:10.1074/jbc.M204279200 PubMedCrossRefGoogle Scholar
  17. 17.
    Natarajan C, Bright JJ (2002) Peroxisome proliferator-activated receptor-γ agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation. Genes Immun 3:59–70. doi:10.1038/sj.gene.6363832 PubMedCrossRefGoogle Scholar
  18. 18.
    Gupta RA, Sarraf P, Brockman JA, Shappell SB, Raftery LA, Willson TM et al (2003) Peroxisome proliferator-activated receptor γ and transforming growth factor-β pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22. J Biol Chem 278:7431–7438. doi:10.1074/jbc.M208076200 PubMedCrossRefGoogle Scholar
  19. 19.
    Tan NS, Michalik L, Noy N, Yasmin R, Pacot C, Heim M et al (2001) Critical roles of PPAR beta/delta in keratinocyte response to inflammation. Genes Dev 15:3263–3277. doi:10.1101/gad.207501 PubMedCrossRefGoogle Scholar
  20. 20.
    Lee SK, Kim HJ, Chi SG, Jang JY, Nam KD, Kim NH et al (2005) Saccharomyces boulardii activates expression of peroxisome proliferator-activated receptor-γ in HT-29 cells. Korean J Gastroenterol 45:328–334PubMedGoogle Scholar
  21. 21.
    Chung SK, Lee MG, Ryu BK, Lee JH, Han J, Byun DS, Chae KS, Lee KY, Jang JY, Kim HJ, Chi SG (2007) Frequent alteration of XAF1 in human colorectal cancers: implication for tumor cell resistance to apoptotic stresses. Gastroenterologia 132:2459–2477. doi:10.1053/j.gastro.2007.04.024 CrossRefGoogle Scholar
  22. 22.
    Medina C, Videla S, Radomski A, Radomski M, Antolin M, Guarner F et al (2001) Therapeutic effect of phenantroline in two rat models of inflammatory bowel disease. Scand J Gastroenterol 36:1314–1319. doi:10.1080/003655201317097182 PubMedCrossRefGoogle Scholar
  23. 23.
    Craig R, Larkin A, Mingo AM, Thuerauf DJ, Andrews C, McDonough PM et al (2000) p38 MAPK and NF-kB collaborate to induce interleukin-6 gene expression and release. Evidence for a cytoprotective autocrine signaling pathway in a cardiac myocyte model system. J Biol Chem 275:23814–23824. doi:10.1074/jbc.M909695199 PubMedCrossRefGoogle Scholar
  24. 24.
    Elson CO, Sartor RB, Tennyson GS, Riddell RH (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367. doi:10.1016/0016-5085(95)90599-5 PubMedCrossRefGoogle Scholar
  25. 25.
    Boismenu R, Chen Y (2000) Insights from mouse models of colitis. J Leukoc Biol 67:267–278PubMedGoogle Scholar
  26. 26.
    Castagliuolo I, LaMont JT, Nikulasson ST, Pothoulakis C (1996) Saccharomyces boulardii protease inhibits Clostridium difficile toxin A effects in the rat ileum. Infect Immun 64:5225–5232PubMedGoogle Scholar
  27. 27.
    Czerucka D, Rampal P (1999) Effect of Saccharomyces boulardii on cAMP- and Ca2+ -dependent Cl- secretion in T84 cells. Dig Dis Sci 44:2359–2368. doi:10.1023/A:1026689628136 PubMedCrossRefGoogle Scholar
  28. 28.
    Fajas L, Auboeuf D, Raspe E, Schoonjans K, Lefebvre AM, Saladin R et al (1997) The organization, promoter analysis, and expression of the human PPARγ gene. J Biol Chem 272:18779–18789. doi:10.1074/jbc.272.30.18779 PubMedCrossRefGoogle Scholar
  29. 29.
    Rosen ED, Spiegelman BM (2001) PPARγ : a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 276:37731–37734. doi:10.1074/jbc.M106424200 PubMedCrossRefGoogle Scholar
  30. 30.
    Chawla A, Barak Y, Nagy L, Liao D, Tontonoz P, Evans RM (2001) PPAR-γ dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat Med 7:48–52. doi:10.1038/83336 PubMedCrossRefGoogle Scholar
  31. 31.
    Kelly D, Campbell JI, King TP, Grant G, Jansson EA, Coutts AG et al (2004) Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-γ and RelA. Nat Immunol 5:104–112. doi:10.1038/ni1018 PubMedCrossRefGoogle Scholar
  32. 32.
    Mercurio F, Manning AM (1999) Multiple signals converging on NF-kB. Curr Opin Cell Biol 11:226–232. doi:10.1016/S0955-0674(99)80030-1 PubMedCrossRefGoogle Scholar
  33. 33.
    Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-kB activity. Annu Rev Immunol 18:621–663. doi:10.1146/annurev.immunol.18.1.621 PubMedCrossRefGoogle Scholar
  34. 34.
    Desreumaux P, Dubuquoy L, Nutten S, Peuchmaur M, Englaro W, Schoonjans K et al (2001) Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor γ (PPARγ) heterodimer. A basis for new therapeutic strategies. J Exp Med 193:827–838. doi:10.1084/jem.193.7.827 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Internal Medicine, Institute of GastroenterologyYonsei University College of MedicineSeoulKorea
  2. 2.Department of Pathology, School of MedicineKyung Hee UniversitySeoulKorea
  3. 3.School of Life Sciences and BiotechnologyKorea UniversitySeoulKorea
  4. 4.Department of Internal Medicine, School of MedicineKyung Hee UniversitySeoulKorea

Personalised recommendations