title: Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2.
abstract: Recent evidence suggests that probiotic bacteria may stabilize gut barrier function via induction of anti-microbial peptides such as defensins. This study aimed to elucidate the induction mechanism of the human beta defensin-2 (hBD-2) gene by different probiotic lactobacillus strains. The expression of hBD-2 mRNA peaked at 6 h of incubation upon treatment of Caco-2 cells and increased with higher dosage of various probiotic bacteria. Deletion of nuclear factor (NF)-kappaB and activator protein-1 (AP-1) binding sites on the hBD-2 promoter resulted in a complete abrogation of promoter activation by probiotics. As revealed by the use of specific mitogen-activated protein kinase (MAPK) inhibitors the hBD-2 induction was dependent on the MAPK extracellular regulated kinase (ERK 1/2), p38 and c-Jun N-terminal kinase (JNK), although to varying degrees. Several Lactobacillus strains and VSL#3, a probiotic cocktail of four lactobacilli, three bifidum and one streptococcus species, induced the secretion of the hBD-2 peptide into the culture media as shown by enzyme-linked immunosorbent assay (ELISA). Thus, the present study suggests that lactobacilli and the VSL#3 bacterial mixture strengthen intestinal barrier functions through the up-regulation of hBD-2 via induction of proinflammatory pathways including NF-kappaB and AP-1 as well as MAPKs.
authors.affiliation: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology and University of Tübingen, Stuttgart, Germany. miriam.schlee@ikp-stuttgart.de
authors.forename: M
authors.initials: M
authors.lastname: Schlee
authors.forename: J
authors.initials: J
authors.lastname: Harder
authors.forename: B
authors.initials: B
authors.lastname: Köten
authors.forename: E F
authors.initials: EF
authors.lastname: Stange
authors.forename: J
authors.initials: J
authors.lastname: Wehkamp
authors.forename: K
authors.initials: K
authors.lastname: Fellermann
mesh_terms: D018938:Caco-2 Cells; D004306:Dose-Response Relationship, Immunologic; D020895:Enterocytes / Q000276:immunology*; D006801:Humans; D007778:Lactobacillus / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics; D019936:Probiotics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: C106641:DEFB4A protein, human; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D023083:beta-Defensins