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Up-Regulation of Intestinal Epithelial Cell Derived IL-7 Expression by Keratinocyte Growth Factor through STAT1/IRF-1, IRF-2 Pathway

BACKGROUND: Epithelial cells(EC)-derived interleukin-7 (IL-7) plays a crucial role in control of development and homeostasis of neighboring intraepithelial lymphocytes (IEL), and keratinocyte growth factor (KGF) exerts protective effects on intestinal epithelial cells and up-regulates EC-derived IL-...

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Autores principales: Cai, Yu-Jiao, Wang, Wen-Sheng, Yang, Yang, Sun, Li-Hua, Teitelbaum, Daniel H., Yang, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595257/
https://www.ncbi.nlm.nih.gov/pubmed/23554911
http://dx.doi.org/10.1371/journal.pone.0058647
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author Cai, Yu-Jiao
Wang, Wen-Sheng
Yang, Yang
Sun, Li-Hua
Teitelbaum, Daniel H.
Yang, Hua
author_facet Cai, Yu-Jiao
Wang, Wen-Sheng
Yang, Yang
Sun, Li-Hua
Teitelbaum, Daniel H.
Yang, Hua
author_sort Cai, Yu-Jiao
collection PubMed
description BACKGROUND: Epithelial cells(EC)-derived interleukin-7 (IL-7) plays a crucial role in control of development and homeostasis of neighboring intraepithelial lymphocytes (IEL), and keratinocyte growth factor (KGF) exerts protective effects on intestinal epithelial cells and up-regulates EC-derived IL-7 expression through KGFR pathway. This study was to further investigate the molecular mechanism involved in the regulation of IL-7 expression by KGF in the intestine. METHODS: Intestinal epithelial cells (LoVo cells) and adult C57BL/6J mice were treated with KGF. Epithelial cell proliferation was studied by flow cytometry for BrdU-incorporation and by immunohistochemistry for PCNA staining. Western blot was used to detect the changes of expression of P-Tyr-STAT1, STAT1, and IL-7 by inhibiting STAT1. Alterations of nuclear extracts and total proteins of IRF-1, IRF-2 and IL-7 following IRF-1 and IRF-2 RNA interference with KGF treatment were also measured with western blot. Moreover, IL-7 mRNA expressions were also detected by Real-time PCR and IL-7 protein level in culture supernatants was measured by enzyme linked immunosorbent assay(ELISA). RESULTS: KGF administration significantly increased LoVo cell proliferation and also increased intestinal wet weight, villus height, crypt depth and crypt cell proliferation in mice. KGF treatment led to increased levels of P-Tyr-STAT1, RAPA and AG490 both blocked P-Tyr-STAT1 and IL-7 expression in LoVo cells. IRF-1 and IRF-2 expression in vivo and in vitro were also up-regulated by KGF, and IL-7 expression was decreased after IRF-1 and IRF-2 expression was silenced by interfering RNA, respectively. CONCLUSION: KGF could up-regulate IL-7 expression through the STAT1/IRF-1, IRF-2 signaling pathway, which is a new insight in potential effects of KGF on the intestinal mucosal immune system.
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spelling pubmed-35952572013-04-02 Up-Regulation of Intestinal Epithelial Cell Derived IL-7 Expression by Keratinocyte Growth Factor through STAT1/IRF-1, IRF-2 Pathway Cai, Yu-Jiao Wang, Wen-Sheng Yang, Yang Sun, Li-Hua Teitelbaum, Daniel H. Yang, Hua PLoS One Research Article BACKGROUND: Epithelial cells(EC)-derived interleukin-7 (IL-7) plays a crucial role in control of development and homeostasis of neighboring intraepithelial lymphocytes (IEL), and keratinocyte growth factor (KGF) exerts protective effects on intestinal epithelial cells and up-regulates EC-derived IL-7 expression through KGFR pathway. This study was to further investigate the molecular mechanism involved in the regulation of IL-7 expression by KGF in the intestine. METHODS: Intestinal epithelial cells (LoVo cells) and adult C57BL/6J mice were treated with KGF. Epithelial cell proliferation was studied by flow cytometry for BrdU-incorporation and by immunohistochemistry for PCNA staining. Western blot was used to detect the changes of expression of P-Tyr-STAT1, STAT1, and IL-7 by inhibiting STAT1. Alterations of nuclear extracts and total proteins of IRF-1, IRF-2 and IL-7 following IRF-1 and IRF-2 RNA interference with KGF treatment were also measured with western blot. Moreover, IL-7 mRNA expressions were also detected by Real-time PCR and IL-7 protein level in culture supernatants was measured by enzyme linked immunosorbent assay(ELISA). RESULTS: KGF administration significantly increased LoVo cell proliferation and also increased intestinal wet weight, villus height, crypt depth and crypt cell proliferation in mice. KGF treatment led to increased levels of P-Tyr-STAT1, RAPA and AG490 both blocked P-Tyr-STAT1 and IL-7 expression in LoVo cells. IRF-1 and IRF-2 expression in vivo and in vitro were also up-regulated by KGF, and IL-7 expression was decreased after IRF-1 and IRF-2 expression was silenced by interfering RNA, respectively. CONCLUSION: KGF could up-regulate IL-7 expression through the STAT1/IRF-1, IRF-2 signaling pathway, which is a new insight in potential effects of KGF on the intestinal mucosal immune system. Public Library of Science 2013-03-12 /pmc/articles/PMC3595257/ /pubmed/23554911 http://dx.doi.org/10.1371/journal.pone.0058647 Text en © 2013 Cai et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Cai, Yu-Jiao
Wang, Wen-Sheng
Yang, Yang
Sun, Li-Hua
Teitelbaum, Daniel H.
Yang, Hua
Up-Regulation of Intestinal Epithelial Cell Derived IL-7 Expression by Keratinocyte Growth Factor through STAT1/IRF-1, IRF-2 Pathway
title Up-Regulation of Intestinal Epithelial Cell Derived IL-7 Expression by Keratinocyte Growth Factor through STAT1/IRF-1, IRF-2 Pathway
title_full Up-Regulation of Intestinal Epithelial Cell Derived IL-7 Expression by Keratinocyte Growth Factor through STAT1/IRF-1, IRF-2 Pathway
title_fullStr Up-Regulation of Intestinal Epithelial Cell Derived IL-7 Expression by Keratinocyte Growth Factor through STAT1/IRF-1, IRF-2 Pathway
title_full_unstemmed Up-Regulation of Intestinal Epithelial Cell Derived IL-7 Expression by Keratinocyte Growth Factor through STAT1/IRF-1, IRF-2 Pathway
title_short Up-Regulation of Intestinal Epithelial Cell Derived IL-7 Expression by Keratinocyte Growth Factor through STAT1/IRF-1, IRF-2 Pathway
title_sort up-regulation of intestinal epithelial cell derived il-7 expression by keratinocyte growth factor through stat1/irf-1, irf-2 pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595257/
https://www.ncbi.nlm.nih.gov/pubmed/23554911
http://dx.doi.org/10.1371/journal.pone.0058647
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