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Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells
Visceral fat accumulation as observed in Crohn's disease and obesity is linked to chronic gut inflammation, suggesting that accumulation of gut adipocytes can trigger local inflammatory signaling. However, direct interactions between intestinal epithelial cells (IECs) and adipocytes have not be...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605307/ https://www.ncbi.nlm.nih.gov/pubmed/28789943 http://dx.doi.org/10.1016/j.ebiom.2017.07.027 |
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author | Takahashi, Yu Sato, Shintaro Kurashima, Yosuke Lai, Chen-Yi Otsu, Makoto Hayashi, Mikio Yamaguchi, Takayuki Kiyono, Hiroshi |
author_facet | Takahashi, Yu Sato, Shintaro Kurashima, Yosuke Lai, Chen-Yi Otsu, Makoto Hayashi, Mikio Yamaguchi, Takayuki Kiyono, Hiroshi |
author_sort | Takahashi, Yu |
collection | PubMed |
description | Visceral fat accumulation as observed in Crohn's disease and obesity is linked to chronic gut inflammation, suggesting that accumulation of gut adipocytes can trigger local inflammatory signaling. However, direct interactions between intestinal epithelial cells (IECs) and adipocytes have not been investigated, in part because IEC physiology is difficult to replicate in culture. In this study, we originally prepared intact, polarized, and cytokine responsive IEC monolayers from primary or induced pluripotent stem cell-derived intestinal organoids by simple and repeatable methods. When these physiological IECs were co-cultured with differentiated adipocytes in Transwell, pro-inflammatory genes were induced in both cell types, suggesting reciprocal inflammatory activation in the absence of immunocompetent cells. These inflammatory responses were blocked by nuclear factor-κB or signal transducer and activator of transcription 3 inhibition and by anti-tumor necrosis factor- or anti-interleukin-6-neutralizing antibodies. Our results highlight the utility of these monolayers for investigating IEC biology. Furthermore, this system recapitulates the intestinal epithelium–mesenteric fat signals that potentially trigger or worsen inflammatory disorders such as Crohn's disease and obesity-related enterocolitis. |
format | Online Article Text |
id | pubmed-5605307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-56053072017-09-26 Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells Takahashi, Yu Sato, Shintaro Kurashima, Yosuke Lai, Chen-Yi Otsu, Makoto Hayashi, Mikio Yamaguchi, Takayuki Kiyono, Hiroshi EBioMedicine Research Paper Visceral fat accumulation as observed in Crohn's disease and obesity is linked to chronic gut inflammation, suggesting that accumulation of gut adipocytes can trigger local inflammatory signaling. However, direct interactions between intestinal epithelial cells (IECs) and adipocytes have not been investigated, in part because IEC physiology is difficult to replicate in culture. In this study, we originally prepared intact, polarized, and cytokine responsive IEC monolayers from primary or induced pluripotent stem cell-derived intestinal organoids by simple and repeatable methods. When these physiological IECs were co-cultured with differentiated adipocytes in Transwell, pro-inflammatory genes were induced in both cell types, suggesting reciprocal inflammatory activation in the absence of immunocompetent cells. These inflammatory responses were blocked by nuclear factor-κB or signal transducer and activator of transcription 3 inhibition and by anti-tumor necrosis factor- or anti-interleukin-6-neutralizing antibodies. Our results highlight the utility of these monolayers for investigating IEC biology. Furthermore, this system recapitulates the intestinal epithelium–mesenteric fat signals that potentially trigger or worsen inflammatory disorders such as Crohn's disease and obesity-related enterocolitis. Elsevier 2017-08-02 /pmc/articles/PMC5605307/ /pubmed/28789943 http://dx.doi.org/10.1016/j.ebiom.2017.07.027 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Takahashi, Yu Sato, Shintaro Kurashima, Yosuke Lai, Chen-Yi Otsu, Makoto Hayashi, Mikio Yamaguchi, Takayuki Kiyono, Hiroshi Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells |
title | Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells |
title_full | Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells |
title_fullStr | Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells |
title_full_unstemmed | Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells |
title_short | Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells |
title_sort | reciprocal inflammatory signaling between intestinal epithelial cells and adipocytes in the absence of immune cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605307/ https://www.ncbi.nlm.nih.gov/pubmed/28789943 http://dx.doi.org/10.1016/j.ebiom.2017.07.027 |
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