Mechanisms involved in alleviation of intestinal inflammation by bifidobacterium breve soluble factors.
OBJECTIVE
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
TNFalpha-induced chemokine (CXCL8) secretion and alteration of NF-kappaB 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-kappaB transcription pathways and implying decreased phosphorylation of p38-MAPK and IkappaB-alpha 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.
Heuvelin
Elise
E
INSERM U793, Paris, France.
Lebreton
Corinne
C
Grangette
Corinne
C
Pot
Bruno
B
Cerf-Bensussan
Nadine
N
Heyman
Martine
M
D000818:Animals; D001644:Bifidobacterium / Q000502:physiology*; D015153:Blotting, Western; D003092:Colitis / Q000517:prevention & control*; D017077:Culture Media, Conditioned; D024202:Electrophoretic Mobility Shift Assay; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D017077:Culture Media, Conditioned; D016209:Interleukin-8; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha