title: The host response to the probiotic Escherichia coli strain Nissle 1917: specific up-regulation of the proinflammatory chemokine MCP-1.
abstract: BACKGROUND
  The use of live microorganisms to influence positively the course of intestinal disorders such as infectious diarrhea or chronic inflammatory conditions has recently gained increasing interest as a therapeutic alternative. In vitro and in vivo investigations have demonstrated that probiotic-host eukaryotic cell interactions evoke a large number of responses potentially responsible for the effects of probiotics. The aim of this study was to improve our understanding of the E. coli Nissle 1917-host interaction by analyzing the gene expression pattern initiated by this probiotic in human intestinal epithelial cells.
  
  
  METHODS
  Gene expression profiles of Caco-2 cells treated with E. coli Nissle 1917 were analyzed with microarrays. A second human intestinal cell line and also pieces of small intestine from BALB/c mice were used to confirm regulatory data of selected genes by real-time RT-PCR and cytometric bead array (CBA) to detect secretion of corresponding proteins.
  
  
  RESULTS
  Whole genome expression analysis revealed 126 genes specifically regulated after treatment of confluent Caco-2 cells with E. coli Nissle 1917. Among others, expression of genes encoding the proinflammatory molecules monocyte chemoattractant protein-1 ligand 2 (MCP-1), macrophage inflammatory protein-2 alpha (MIP-2alpha) and macrophage inflammatory protein-2 beta (MIP-2beta) was increased up to 10 fold. Caco-2 cells cocultured with E. coli Nissle 1917 also secreted high amounts of MCP-1 protein. Elevated levels of MCP-1 and MIP-2alpha mRNA could be confirmed with Lovo cells. MCP-1 gene expression was also up-regulated in mouse intestinal tissue.
  
  
  CONCLUSIONS
  Thus, probiotic E. coli Nissle 1917 specifically upregulates expression of proinflammatory genes and proteins in human and mouse intestinal epithelial cells.
authors.affiliation: German Research Centre for Biotechnology, Mucosal Immunity Group, Mascheroder Weg 1, 38124 Braunschweig, Germany. suk@gbf.de
authors.forename: Sya N
authors.initials: SN
authors.lastname: Ukena
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Westendorf
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hansen
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.forename: Sina
authors.initials: S
authors.lastname: Coldewey
authors.forename: Sebastian
authors.initials: S
authors.lastname: Suerbaum
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.forename: Florian
authors.initials: F
authors.lastname: Gunzer
mesh_terms: D001691:Biological Therapy / Q000379:methods*; D018938:Caco-2 Cells; D018932:Chemokine CCL2 / Q000235:genetics*; D054426:Chemokine CXCL2; D004926:Escherichia coli / Q000166:cytology / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D007167:Immunotherapy; D007249:Inflammation / Q000235:genetics; D007410:Intestinal Diseases / Q000628:therapy; D007422:Intestines / Q000166:cytology / Q000276:immunology; D015846:Monokines / Q000235:genetics; D019936:Probiotics; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D015846:Monokines; D012333:RNA, Messenger