title: Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-kappaB-mediated IL-8 gene expression.
abstract: Saccharomyces boulardii (Sb) is a non-pathogenic yeast that ameliorates intestinal injury and inflammation caused by a wide variety of enteric pathogens. We hypothesized that Sb may exert its probiotic effects by modulation of host cell signaling and pro-inflammatory gene expression. Human HT-29 colonocytes and THP-1 monocytes were stimulated with IL-1beta, TNFalpha or LPS in the presence or absence of Sb culture supernatant (SbS). IL-8 protein and mRNA levels were measured by ELISA and RT-PCR, respectively. The effect of SbS on IkappaB alpha degradation was studied by Western blotting and on NF-kappaB-DNA binding by EMSA. NF-kappaB-regulated gene expression was evaluated by transient transfection of THP-1 cells with a NF-kappaB-responsive luciferase reporter gene. SbS inhibited IL-8 protein production in IL-1beta or TNFalpha stimulated HT-29 cells (by 75% and 85%, respectively; P<0.001) and prevented IL-1beta-induced up-regulation of IL-8 mRNA. SbS also inhibited IL-8 production, prevented IkappaB alpha degradation, and reduced both NF-kappaB-DNA binding and NF-kappaB reporter gene up-regulation in IL-1beta or LPS-stimulated THP-1 cells. Purification and characterization studies indicate that the S. boulardii anti-inflammatory factor (SAIF) is small (<1 kDa), heat stable, and water soluble. The probiotic yeast Saccharomyces boulardii exerts an anti-inflammatory effect by producing a low molecular weight soluble factor that blocks NF-kappaB activation and NF-kappaB-mediated IL-8 gene expression in intestinal epithelial cells and monocytes. SAIF may mediate, at least in part, the beneficial effects of Saccharomyces boulardii in infectious and non-infectious human intestinal disease.
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Stavros
authors.initials: S
authors.lastname: Sougioultzis
authors.forename: Simos
authors.initials: S
authors.lastname: Simeonidis
authors.forename: K Ramakrishnan
authors.initials: KR
authors.lastname: Bhaskar
authors.forename: Xinhua
authors.initials: X
authors.lastname: Chen
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Anton
authors.forename: Sarah
authors.initials: S
authors.lastname: Keates
authors.forename: Charalabos
authors.initials: C
authors.lastname: Pothoulakis
authors.forename: Ciarán P
authors.initials: CP
authors.lastname: Kelly
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006358:Hot Temperature; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D012440:Saccharomyces / Q000378:metabolism*; D012995:Solubility; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D011134:Polysaccharides; D051996:Transcription Factor RelA; D004247:DNA