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Mechanisms involved in alleviation of inflammation by Bifidobacterium breve soluble factors

Abstract : Objectives Soluble factors released by Bifidobacterium breve C50 (Bb) alleviate the secretion of pro-inflammatory cytokines by immune cells, but their effect on intestinal epithelium remains elusive. To decipher the mechanisms accounting for the cross-talk between bacteria/soluble factors and intestinal epithelium, we measured the capacity of the bacteria, its conditioned medium (Bb-CM) and other Gram(+) commensal bacteria to dampen inflammatory chemokine secretion. Methods TNFα-induced chemokine (CXCL8) secretion and alteration of NF-κB and AP-1 signalling pathways by Bb were studied by EMSA, confocal microscopy and western blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS-induced colitis in mice. Results Bb and Bb-CM, but not other commensal bacteria, induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial cells driven by both AP-1 and NF-κB transcription pathways and implying decreased phosphorylation of p38-MAPK and IκB-α molecules. In TNBS-induced colitis in mice, Bb-CM decreased the colitis score and inflammatory cytokine expression, an effect reproduced by dendritic cell conditioning with Bb-CM. Conclusions Bb and secreted soluble factors contribute positively to intestinal homeostasis by attenuating chemokine production. The results indicate that Bb down regulate inflammation at the epithelial level by inhibiting phosphorylations involved in inflammatory processes and by protective conditioning of dendritic cells.
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Submitted on : Monday, June 8, 2009 - 9:21:37 AM
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Elise Heuvelin, Corinne Lebreton, Corinne Grangette, Bruno Pot, Nadine Cerf-Bensussan, et al.. Mechanisms involved in alleviation of inflammation by Bifidobacterium breve soluble factors. PLoS ONE, Public Library of Science, 2009, 4(4) (e5184), pp.e5184. ⟨10.1371/journal.pone.0005184⟩. ⟨inserm-00392418⟩



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