Neutrophil gelatinase‐associated lipocalin regulates gut microbiota of mice

Mori, Kota; Suzuki, Takeshi; Minamishima, Shizuka; Igarashi, Toru; Irie, Kazunari; Nishimura, Daisuke; Seki, Hiroyuki; Yamada, Takashige; Kosugi, Shizuko; Katori, Nobuyuki; Hashiguchi, Saori; Morisaki, Hiroshi

doi:10.1111/jgh.13042

Cited by 15 publications

(15 citation statements)

References 31 publications

(53 reference statements)

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“…Neutrophils are the first cells of the immune system to increase in the MLN and are recruited to the adipose tissue and ILP by an inflammatory process after HFD. The presence of neutrophils in adipose tissue occurs after 3 days of HFD, indicating that this recruitment occurs rapidly and transiently and contributes to the maintenance of a homeostatic microbiota in the gut, as recently reported …”

Section: Discussionsupporting

confidence: 71%

Interleukin‐17/interleukin‐17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high‐fat diet‐induced metabolic syndrome model

Pérez¹,

Martins²,

Dias³

et al. 2018

Immunology

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Sound evidence supports a role for interleukin-17 (IL-17) -producing cd T cells and IL-17-producing helper T (Th17) cells in intestinal homeostasis, especially in intestinal barrier integrity. In the present study, we aimed to evaluate the role of IL-17 cytokine in the regulation of intestinal immunity and obesity-induced metabolic syndrome (MetS) in an experimental murine model. C57BL/6 wild-type (WT) mice and mice lacking the IL-17 cytokine receptor (IL-17RA À/À ) were fed either a control diet (CD) or a high-fat diet (HFD) for 9 weeks. Our data demonstrate that IL-17RA À/À mice are protected against obesity, but develop hyperglycemia, hyperinsulinemia and insulin resistance. In parallel, HFD-fed IL-17RA À/À mice display intense inflammation in the ileum compared with WT mice on the HFD. IL-17RA À/À mice fed the HFD exhibit impaired neutrophil migration to the intestinal mucosa and reduced gene expression of the CXCL-1 chemokine and CXCR-2 receptor in the ileum. Interestingly, the populations of neutrophils (CD11b + Ly6G + ) and anti-inflammatory macrophages (CD11b + CX3CR1 + ) are increased in the mesenteric lymph nodes of these mice. IL-17RA À/À mice on the HFD also display increased commensal bacterial translocation into the bloodstream and elevated lipopolysaccharide (LPS) levels in the visceral adipose tissue (VAT). Metagenomic analysis of bacterial 16S gene revealed increased Proteobacteria and Bacteroidetes phyla, the main representatives of Gram-negative bacteria, and reduced Akkermansia muciniphila in the fecal samples of IL-17RA À/À mice fed the HFD. Together, these data indicate that the IL-17/IL-17R axis drives intestinal neutrophil migration, limits gut dysbiosis and attenuates LPS translocation to VAT, resulting in protection to MetS.

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Section: Discussionsupporting

confidence: 71%

Interleukin‐17/interleukin‐17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high‐fat diet‐induced metabolic syndrome model

Pérez¹,

Martins²,

Dias³

et al. 2018

Immunology

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“…A decade ago, the production and expression of Lcn2 in the intestinal epithelium was demonstrated in a rhesus macaque model of bacterial infection [23] and by administration of indomethacin in mice [24]. Using a murine model of LPS-induced endotoxemia, we further confirmed the presence of Lcn2 in the intestinal crypt cells under physiological conditions and demonstrated the existence of correlations between the severity of illness in critically ill individuals and the accumulation of Lcn2 in the crypt lamina of the ileum and colon and its discharge into the intestinal lumen, the first scene of gut-origin sepsis [25].…”

Section: Expression and Modulation Of Lcn2 In Gut-origin Sepsismentioning

confidence: 58%

Functions and regulation of lipocalin-2 in gut-origin sepsis: a narrative review

Irie

Kato

et al. 2019

Crit Care

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Lipocalin-2 (Lcn2), an innate immune protein, has come to be recognized for its roles in iron homeostasis, infection, and inflammation. In this narrative review, we provide a comprehensive description based on currently available evidence of the clinical implications of Lcn2 and its therapeutic potency in gut-origin sepsis. Lcn2 appears to mitigate gut barrier injury via maintaining homeostasis of the microbiota and exerting antioxidant strategy, as well as by deactivating macrophages and inducing immune cell apoptosis to terminate systemic hyper-inflammation. We propose that development of a therapeutic strategy targeting lipocalin-2 could be highly promising in the management of gut-origin sepsis.

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“…However, the pathogenic bacterial population could be kept at bay by increased levels of KC that may facilitate infiltration of neutrophils. Microbiota homeostasis in the intestinal mucosal tissue is proposed to be maintained by neutrophil gelatinase‐associated lipocalin protein (Mori et al, ). Thus, it is enticing to postulate that KC could be a very significant player to distinguish TCE‐mediated gut‐associated responses during continuous exposure or exposure cessation.…”

Section: Discussionmentioning

confidence: 99%

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

Khare

Gokulan

Williams

et al. 2018

J of Applied Toxicology

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The developing immune system is particularly sensitive to immunotoxicants. This study assessed trichloroethylene (TCE)-induced effects on the gut microbiome and cytokine production during the development in mice. Mice were exposed to TCE (0.05 or 500 μg/mL) at the levels that approximate to environmental or occupational exposure, respectively. Mice were subjected to a continuous developmental exposure to these doses encompassing gestation, lactation and continuing directly in the drinking water postnatally for 154 days (PND154) or PND259. To observe persistence of the effect TCE was removed from the drinking water in a subset of mice on PND154 and were provided regular drinking water until the study terminus (PND259). Abundance of total tissue-associated bacteria reduced only in mice exposed to TCE until PND259. The ratio of Firmicutes/Bacteroidetes did not alter during this continuos exposure; however, cessation of high-dose TCE at PND154 resulted in the increased abundance Bacteroidetes at PND259. Furthermore, high-dose TCE exposure until PND259 resulted in a lower abundance of the genera Bacteroides and Lactobaccilus and increased abundance of genus Bifidobactrium and bacterial family Enterobacteriaceae. TCE exposure until PND154 showed significant changes in the production of interleukin-33; that might play a dual role in maintaining the balance and homeostasis between commensal microbiota and mucosal health. At PND259, interleukin-3, granulocyte-macrophage colony-stimulating factor and Eotaxin were altered in both, the continuous exposure and cessation groups, whereas only a cessation group had a higher level of KC that may facilitate infiltration of neutrophils. The irreversible effects of TCE after a period of exposure cessation suggested a unique programming and potential toxicity of TCE even at the environmental level exposure.

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Neutrophil gelatinase‐associated lipocalin regulates gut microbiota of mice

Abstract: 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.

Cited by 15 publications

References 31 publications

Interleukin‐17/interleukin‐17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high‐fat diet‐induced metabolic syndrome model

Interleukin‐17/interleukin‐17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high‐fat diet‐induced metabolic syndrome model

Functions and regulation of lipocalin-2 in gut-origin sepsis: a narrative review

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

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