title: Neutrophil gelatinase-associated lipocalin regulates gut microbiota of mice.
abstract: OBJECTIVE
  Because neutrophil gelatinase-associated lipocalin (NGAL) is known to provide significant bacteriostatic effects during infectious conditions, we tested the hypothesis that this protein is up-regulated and secreted into the intraluminal cavity of the gut under critically ill conditions and is thus responsible for the regulation of bacterial overgrowth.
  
  
  METHODS
  With our institutional approval, male C57BL/6J mouse (6-7 weeks) were enrolled and applied for lipopolysaccharide or peritonitis model compared with naïve control. We assessed NGAL protein concentrations in intestinal lumen and up-regulation of NGAL expression in intestinal tissues in in vivo as well as ex vivo settings. Simultaneously, we examined the effects of NGAL protein administration on the growth of Escherichia coli (E. coli) in in vivo and in vitro experimental settings. The localization of NGAL in intestinal tissues and lumen was also assessed by immunohistological approach using NGAL antibody.
  
  
  RESULTS
  Both lipopolysaccharide and peritonitis insults evoked the marked up-regulation of NGAL mRNA and protein levels in gut tissues such as crypt cells. In addition, the administration of NGAL protein significantly inhibited the outgrowth of enteric E. coli under both in vitro and in vivo conditions, accompanied by histological evidence.
  
  
  CONCLUSIONS
  Neutrophil gelatinase-associated lipocalin protein accompanied by apparent bacteriostatic action accumulated in the intestinal wall and streamed into the mucosal layer during critically ill state, thereby possibly shaping microbiota homeostasis in the gut.
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.|Japan Society of the Promotion of Science, Tokyo, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Minamishima
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nishimura
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takashige
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Kosugi
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katori
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Hashiguchi
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morisaki
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D016638:Critical Illness; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000254:growth & development; D015870:Gene Expression; D006706:Homeostasis / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D008070:Lipopolysaccharides; D008297:Male; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects* / Q000502:physiology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D010538:Peritonitis / Q000382:microbiology; D015854:Up-Regulation
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D008070:Lipopolysaccharides; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse
keywords: bacteria; gut; lipocalin-2; microbiota; toll-like receptor.