title: Lactobacillus fermentum attenuates the proinflammatory effect of Yersinia enterocolitica on human epithelial cells.
abstract: BACKGROUND
  Lactobacilli represent a major component of the human microbiota. In this study we investigated whether and how Lactobacillus fermentum inhibits the proinflammatory responses of human epithelial cells on Yersinia enterocolitica infection.
  
  
  METHODS
  Human epithelial cells were exposed to Y. enterocolitica pYV(-) or L. fermentum or to both strains, combinations of heat-killed L. fermentum or supernatant of L. fermentum cultures and Y. enterocolitica. The modulation of Y. enterocolitica induced IL-8 levels in the culture supernatants was determined and activation of Rac, p38, and NF-kappaB was investigated.
  
  
  RESULTS
  Exposure of human epithelial cells to L. fermentum does not induce NF-kappaB activation and subsequent IL-8 secretion in HeLa cells, whereas Y. enterocolitica induces NF-kappaB activation and high levels of IL-8. Viable L. fermentum, supernatant of L. fermentum cultures, but not heat-killed L. fermentum, inhibited IL-8 secretion of HeLa cells triggered by Y. enterocolitica. Lactobacillus fermentum-exposed HeLa cells showed decreased Rac, p38, and NF-kappaB activation after Y. enterocolitica infection. Treatment of L. fermentum supernatants with phospholipase C abolished the inhibitory effect, indicating that a secreted phospholipid mediates the antiinflammatory properties of L. fermentum. Adhesion to or invasion of Y. enterocolitica into epithelial cells was not altered by coincubation with L. fermentum.
  
  
  CONCLUSIONS
  Our results lead to the conclusion that L. fermentum inhibits the Y. enterocolitica-induced IL-8 production by a possibly secreted phospholipid of <10 kDa molecular weight. These data suggest that L. fermentum may have probiotic properties modulating intestinal inflammatory responses and might offer new therapeutic strategies in the treatment of intestinal inflammatory diseases.
authors.affiliation: Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany. julia-stefanie.frick@med.uni-tuebingen.de
authors.forename: Julia-Stefanie
authors.initials: JS
authors.lastname: Frick
authors.forename: Katrin
authors.initials: K
authors.lastname: Schenk
authors.forename: Matteo
authors.initials: M
authors.lastname: Quitadamo
authors.forename: Frauke
authors.initials: F
authors.lastname: Kahl
authors.forename: Martin
authors.initials: M
authors.lastname: Köberle
authors.forename: Erwin
authors.initials: E
authors.lastname: Bohn
authors.forename: Martin
authors.initials: M
authors.lastname: Aepfelbacher
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
mesh_terms: D001422:Bacterial Adhesion; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D019286:Endopeptidase K / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology*; D020404:Glycerophospholipids / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation; D018836:Inflammation Mediators / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D058085:Iron Compounds / Q000494:pharmacology; D052197:Limosilactobacillus fermentum / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D015009:Yersinia Infections / Q000378:metabolism*; D015008:Yersinia enterocolitica / Q000472:pathogenicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D020404:Glycerophospholipids; D018836:Inflammation Mediators; D016209:Interleukin-8; D058085:Iron Compounds; D016328:NF-kappa B; D048051:p38 Mitogen-Activated Protein Kinases; D019286:Endopeptidase K; D020830:rac1 GTP-Binding Protein