title: Lipocalin 2 prevents intestinal inflammation by enhancing phagocytic bacterial clearance in macrophages.
abstract: 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.
authors.affiliation: Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Toyonaga
authors.affiliation: Department of Gastroenterology &Hepatology, Graduate School of Medicine, Kyoto University, 54 shogoin, Kawahara-cho, Sakyo-ku, Kyoto, 606-8397, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Matsuura
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Gastroenterology &Hepatology, Graduate School of Medicine, Kyoto University, 54 shogoin, Kawahara-cho, Sakyo-ku, Kyoto, 606-8397, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Honzawa
authors.affiliation: Department of Gastroenterology &Hepatology, Graduate School of Medicine, Kyoto University, 54 shogoin, Kawahara-cho, Sakyo-ku, Kyoto, 606-8397, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Minami
authors.affiliation: Department of Gastroenterology &Hepatology, Graduate School of Medicine, Kyoto University, 54 shogoin, Kawahara-cho, Sakyo-ku, Kyoto, 606-8397, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.affiliation: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics / Q000382:microbiology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000502:physiology*; D055786:Gene Knockout Techniques; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D000071068:Lipocalin-2 / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis
chemical_list: C556062:IL10 protein, mouse; D000071068:Lipocalin-2; C071332:Lcn2 protein, mouse; D016753:Interleukin-10