title: Advanced application of bovine intestinal epithelial cell line for evaluating regulatory effect of lactobacilli against heat-killed enterotoxigenic Escherichia coli-mediated inflammation.
abstract: BACKGROUND
  Previously, a bovine intestinal epithelial cell line (BIE cells) was successfully established. This work hypothesized that BIE cells are useful in vitro model system for the study of interactions of microbial- or pathogen-associated molecular patterns (MAMPs or PAMPs) with bovine intestinal epithelial cells and for the selection of immunoregulatory lactic acid bacteria (LAB).
  
  
  RESULTS
  All toll-like receptor (TLR) genes were expressed in BIE cells, being TLR4 one of the most strongly expressed. We demonstrated that heat-stable PAMPs of enterotoxigenic Escherichia coli (ETEC) significantly enhanced the production of IL-6, IL-8, IL-1α and MCP-1 in BIE cells by activating both NF-κB and MAPK pathways. We evaluated the capacity of several lactobacilli strains to modulate heat-stable ETEC PAMPs-mediated inflammatory response in BIE cells. Among these strains evaluated, Lactobacillus casei OLL2768 attenuated heat-stable ETEC PAMPs-induced pro-inflammatory response by inhibiting NF-κB and p38 signaling pathways in BIE cells. Moreover, L. casei OLL2768 negatively regulated TLR4 signaling in BIE cells by up-regulating Toll interacting protein (Tollip) and B-cell lymphoma 3-encoded protein (Bcl-3).
  
  
  CONCLUSIONS
  BIE cells are suitable for the selection of immunoregulatory LAB and for studying the mechanisms involved in the protective activity of immunobiotics against pathogen-induced inflammatory damage. In addition, we showed that L. casei OLL2768 functionally modulate the bovine intestinal epithelium by attenuating heat-stable ETEC PAMPs-induced inflammation. Therefore L. casei OLL2768 is a good candidate for in vivo studying the protective effect of LAB against intestinal inflammatory damage induced by ETEC infection or heat-stable ETEC PAMPs challenge in the bovine host.
authors.affiliation: Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Aoba-ku, 981-8555, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Takanashi
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Tomosada
authors.forename: Julio
authors.initials: J
authors.lastname: Villena
authors.forename: Kozue
authors.initials: K
authors.lastname: Murata
authors.forename: Takuya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Eriko
authors.initials: E
authors.lastname: Chiba
authors.forename: Masanori
authors.initials: M
authors.lastname: Tohno
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shimazu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Aso
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Suda
authors.forename: Shuji
authors.initials: S
authors.lastname: Ikegami
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itoh
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawai
authors.forename: Tadao
authors.initials: T
authors.lastname: Saito
authors.forename: Susana
authors.initials: S
authors.lastname: Alvarez
authors.forename: Haruki
authors.initials: H
authors.lastname: Kitazawa
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology* / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D018836:Inflammation Mediators / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators