Lipocalin 2 prevents intestinal inflammation by enhancing phagocytic bacterial clearance in macrophages
Open accessAbstract
Lipocalin 2 (Lcn2), also called neutrophil gelatinase B-associated lipocalin (NGAL), is an anti-microbial peptide originally identified in neutrophil granules. Although Lcn2/NGAL expression is increased in the inflamed intestinal tissues of patients with inflammatory bowel disease, the role of Lcn2/NGAL in the development of intestinal inflammation remains unclear. Here we investigated the role of Lcn2/NGAL in intestinal inflammation using a spontaneous mouse colitis model, interleukin-10 knock out (IL-10 KO) mice. Lcn2 expression in the colonic tissues of IL-10 KO mice increased with the development of colitis. Lcn2/IL-10 double-KO mice showed a more rapid onset and development of colitis compared to IL-10 KO mice. Lcn2 enhanced phagocytic bacterial clearance in macrophages in vitro after infection with Escherichia coli. Transfer of Lcn2-repleted macrophages prevented the development of colitis in Lcn2/IL-10 double-KO mice in vivo. Our findings revealed that Lcn2 prevents the development of intestinal inflammation. One crucial factor seems to be the enhancement of phagocytic bacterial clearance in macrophages by Lcn2.
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By binding enterobactin, NGAL maintains the balance between commensal bacteria and immune cells in the gut where colitogenic bacteria can reside and secrete high amounts of enterobactin into the intestinal lumen.
“In doing so, NGAL maintains the balance between commensal bacteria and immune cells in the gut where colitogenic bacteria can reside and secrete high amounts of enterobactin into the intestinal lumen (Deriu et al., 2013;Moschen et al., 2016;Toyonaga et al., 2016).”
From Iron in infection and immunity (2020) · cites this paper as Toyonaga et al., 2016
The Discussion (page unavailable) says Lcn2/NGAL regulates mucosal immune responses toward enteric commensal bacteria and prevents colitis in IL-10-deficient mice. The introductory passage (page unavailable) describes sequestration of iron-laden bacterial siderophores, but our copy does not identify enterobactin or say that colitogenic bacteria secrete high amounts of it into the intestinal lumen. (LLM, conf=0.88)
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- Authors
- Toyonaga, T., Matsuura, M., Mori, K., Honzawa, Y., Minami, N., Yamada, S., Kobayashi, T., Hibi, T., & Nakase, H.
- Affiliations
- Kitasato Institute Hospital (JP)
- Kyoto University (JP)
- Shizuoka University (JP)
- Sapporo Medical University (JP)
- Corresponding author
- Nakase, Hiroshi
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-10-13
- Volume
- 6
- Issue
- 1
- Pages
- 35014-35014
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5062163
- OpenAlex
- W2529902668
- Cited by
- 75
- References
- 49
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 8 · 2023: 5 · 2022: 9 · 2021: 13 · 2020: 14 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 1
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
- Funders
- Ministry of Health, Labour and Welfare
- Japan Society for the Promotion of Science (26893122, 24590941, 16K09324, 16K19150, 23590940, 16K19365, 26460967)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- neutrophil gelatinase-associated lipocalin, intestinal inflammation, colitis, macrophages, IL-10, Escherichia coli infection, inflammatory bowel disease
- MeSH terms
- Lipocalin-2, Animals, Colitis, Disease Models, Animal, Escherichia coli, Humans, Macrophages, Phagocytosis, Interleukin-10, Mice, Knockout, Mice, Gene Knockout Techniques
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