Neutrophil gelatinase-associated lipocalin regulates gut microbiota of mice

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background and Aim: 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 (6-7weeks) 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)145-154
Number of pages10
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume31
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Proteins
Peritonitis
Critical Illness
Lipopolysaccharides
Up-Regulation
Escherichia coli
Lipocalin-2
Gastrointestinal Microbiome
Microbiota
Inbred C57BL Mouse
Homeostasis
Messenger RNA
Antibodies
Growth
In Vitro Techniques

Keywords

  • Bacteria
  • Gut
  • Lipocalin-2
  • Microbiota
  • Toll-like receptor

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

@article{7bbf086be82c4057b7dcaa8d984b7121,
title = "Neutrophil gelatinase-associated lipocalin regulates gut microbiota of mice",
abstract = "Background and Aim: 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 (6-7weeks) were enrolled and applied for lipopolysaccharide or peritonitis model compared with na{\"i}ve 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. Conclusion: 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.",
keywords = "Bacteria, Gut, Lipocalin-2, Microbiota, Toll-like receptor",
author = "Katsuya Mori and Takeshi Suzuki and Shizuka Minamishima and Toru Igarashi and Kei Inoue and Daisuke Nishimura and Hiroyuki Seki and Takashige Yamada and Shizuko Kosugi and Nobuyuki Katori and Saori Hashiguchi and Hiroshi Morisaki",
year = "2016",
month = "1",
day = "1",
doi = "10.1111/jgh.13042",
language = "English",
volume = "31",
pages = "145--154",
journal = "Journal of Gastroenterology and Hepatology (Australia)",
issn = "0815-9319",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Neutrophil gelatinase-associated lipocalin regulates gut microbiota of mice

AU - Mori, Katsuya

AU - Suzuki, Takeshi

AU - Minamishima, Shizuka

AU - Igarashi, Toru

AU - Inoue, Kei

AU - Nishimura, Daisuke

AU - Seki, Hiroyuki

AU - Yamada, Takashige

AU - Kosugi, Shizuko

AU - Katori, Nobuyuki

AU - Hashiguchi, Saori

AU - Morisaki, Hiroshi

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background and Aim: 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 (6-7weeks) 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. Conclusion: 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.

AB - Background and Aim: 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 (6-7weeks) 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. Conclusion: 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.

KW - Bacteria

KW - Gut

KW - Lipocalin-2

KW - Microbiota

KW - Toll-like receptor

UR - http://www.scopus.com/inward/record.url?scp=84956923108&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84956923108&partnerID=8YFLogxK

U2 - 10.1111/jgh.13042

DO - 10.1111/jgh.13042

M3 - Article

C2 - 26189649

AN - SCOPUS:84956923108

VL - 31

SP - 145

EP - 154

JO - Journal of Gastroenterology and Hepatology (Australia)

JF - Journal of Gastroenterology and Hepatology (Australia)

SN - 0815-9319

IS - 1

ER -