| Literature DB >> 27078067 |
Alexander R Moschen1, Romana R Gerner2, Jun Wang3, Victoria Klepsch4, Timon E Adolph2, Simon J Reider2, Hubert Hackl5, Alexandra Pfister2, Johannes Schilling6, Patrizia L Moser7, Sarah L Kempster8, Alexander Swidsinski6, Dorothea Orth Höller9, Günter Weiss10, John F Baines3, Arthur Kaser8, Herbert Tilg11.
Abstract
High mucosal and fecal concentrations of the antimicrobial siderophore-binding peptide Lipocalin-2 (Lcn2) are observed in inflammatory bowel disease. However, Lcn2 function in chronic intestinal inflammation remains unclear. Here, we demonstrate that Lcn2 protects from early-onset colitis and spontaneous emergence of right-sided colonic tumors resulting from IL-10 deficiency. Exacerbated inflammation in Lcn2(-/-)/Il10(-/-) mice is driven by IL-6, which also controls tumorigenesis. Lcn2(-/-)/Il10(-/-) mice exhibit profound alterations in gut microbial composition, which contributes to inflammation and tumorigenesis, as demonstrated by the transmissibility of the phenotype and protection conferred by antibiotics. Specifically, facultative pathogenic Alistipes spp. utilize enterobactin as iron source, bloom in Lcn2(-/-)/Il10(-/-) mice, and are sufficient to induce colitis and right-sided tumors when transferred into Il10(-/-) mice. Our results demonstrate that Lcn2 protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota.Entities:
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Year: 2016 PMID： 27078067 DOI： 10.1016/j.chom.2016.03.007
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023