Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-κB-mediated IL-8 gene expression
Section snippets
Cells and reagents
Human transformed monocytic (THP-1), colonic epithelial (HT-29), and gastric epithelial (AGS) cells were obtained from ATCC (American Type Culture Collection, Rockville, MD) and grown in RPMI 1640 media (Gibco-BRL). Recombinant human (rh) IL-1β and TNFα were purchased from R&D Systems (Minneapolis, MN). Purified LPS from E. coli 055:B5 was from Sigma (St. Louis, MO). Anti-human IκBα was obtained from Santa Cruz Biotechnology (Santa Cruz, CA), and anti-NF-κB p65 was from Boehringer Mannheim
S. boulardii supernatant inhibits IL-8 secretion by cytokine-stimulated human colonic and gastric epithelial cell lines, the active component being less than 10 kDa in size
HT-29 cells were serum starved overnight and then stimulated with IL-1β (10 ng/ml), TNF-α (10 ng/ml) or LPS (100 ng/ml), in the presence or absence of SbS (1:1, v/v). After 12 h incubation, the cell conditioned media were collected and IL-8 protein levels measured by ELISA. As illustrated in Fig. 1A resting HT-29 monolayers released little IL-8 protein while stimulation with IL-1β or TNFα markedly increased IL-8 protein production. The presence of SbS significantly reduced IL-8 production in both
Discussion
We report here that the yeast Saccharomyces boulardii, a probiotic widely used to treat or prevent a variety of human diarrheal diseases, produces SAIF (Saccharomyces anti-inflammatory factor) a small molecular weight, water soluble molecule that inhibits the activation of NF-κB, a transcription factor that plays a central role in human inflammatory responses. The mechanism of NF-κB inhibition exerted by SAIF involves inhibition of IκBα degradation, thereby resulting in sequestration of NF-κB
Acknowledgments
The authors are grateful to Amy Pan, B.Sc., Michel Warny, M.D., Ph.D., and Samer Aboudola M.D. for their contributions.
Sponsor. This work was supported in part by a grant from Biocodex Laboratories, Montrouge, France and NIH Grant DK 33506.
Competing interests statement. Drs. Sougioultzis, Bhaskar, Pothoulakis, and Kelly are named co-inventors on a patent application on Saccharomyces anti-inflammatory factor (SAIF) filed by Beth Israel Deaconess Medical Center, Boston, MA.
Dr. Pothoulakis has
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These authors contributed equally to this work.