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TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor

Proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) is a crucial effector of immune responses in the brain that participates in the pathogenesis of several acute and chronic neurodegenerative disorders. Accumulating evidence has suggested that TNF-α negatively regulates embryonic and adult...

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Autores principales: Lan, Xiqian, Chen, Qiang, Wang, Yongxiang, Jia, Beibei, Sun, Lijun, Zheng, Jialin, Peng, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517586/
https://www.ncbi.nlm.nih.gov/pubmed/23236394
http://dx.doi.org/10.1371/journal.pone.0050783
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author Lan, Xiqian
Chen, Qiang
Wang, Yongxiang
Jia, Beibei
Sun, Lijun
Zheng, Jialin
Peng, Hui
author_facet Lan, Xiqian
Chen, Qiang
Wang, Yongxiang
Jia, Beibei
Sun, Lijun
Zheng, Jialin
Peng, Hui
author_sort Lan, Xiqian
collection PubMed
description Proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) is a crucial effector of immune responses in the brain that participates in the pathogenesis of several acute and chronic neurodegenerative disorders. Accumulating evidence has suggested that TNF-α negatively regulates embryonic and adult neurogenesis. However, the effect of TNF-α on cell fate decision in human neural progenitor cells (NPCs) has rarely been studied. Our previous studies have shown that recombinant TNF-α enhances astrogliogenesis and inhibits neurogenesis of human NPCs through the STAT3 (signal transducer and activator of transcription 3) pathway. In the current study, we further elucidated the specific mechanism involved in TNF-α-induced astrogliogenesis. We found that TNF-α activated STAT3 at delayed time points (6 h and 24 h), whereas conditioned medium collected from TNF-α-treated NPCs induced an immediate STAT3 activation. These data suggest TNF-α plays an indirect role on STAT3 activation and the subsequent NPC differentiation. Further, we showed that TNF-α induced abundant amounts of the IL-6 family cytokines, including Leukemia inhibitory factor (LIF) and Interleukin 6 (IL-6), in human NPCs. TNF-α-induced STAT3 phosphorylation and astrogliogenesis were abrogated by the addition of neutralizing antibody for LIF, but not for IL-6, revealing a critical role of autocrine secretion of LIF in TNF-α-induced STAT3 activation and astrogliogenesis. This study generates important data elucidating the role of TNF-α in neurogenesis and may provide insight into new therapeutic strategies for brain inflammation.
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spelling pubmed-35175862012-12-12 TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor Lan, Xiqian Chen, Qiang Wang, Yongxiang Jia, Beibei Sun, Lijun Zheng, Jialin Peng, Hui PLoS One Research Article Proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) is a crucial effector of immune responses in the brain that participates in the pathogenesis of several acute and chronic neurodegenerative disorders. Accumulating evidence has suggested that TNF-α negatively regulates embryonic and adult neurogenesis. However, the effect of TNF-α on cell fate decision in human neural progenitor cells (NPCs) has rarely been studied. Our previous studies have shown that recombinant TNF-α enhances astrogliogenesis and inhibits neurogenesis of human NPCs through the STAT3 (signal transducer and activator of transcription 3) pathway. In the current study, we further elucidated the specific mechanism involved in TNF-α-induced astrogliogenesis. We found that TNF-α activated STAT3 at delayed time points (6 h and 24 h), whereas conditioned medium collected from TNF-α-treated NPCs induced an immediate STAT3 activation. These data suggest TNF-α plays an indirect role on STAT3 activation and the subsequent NPC differentiation. Further, we showed that TNF-α induced abundant amounts of the IL-6 family cytokines, including Leukemia inhibitory factor (LIF) and Interleukin 6 (IL-6), in human NPCs. TNF-α-induced STAT3 phosphorylation and astrogliogenesis were abrogated by the addition of neutralizing antibody for LIF, but not for IL-6, revealing a critical role of autocrine secretion of LIF in TNF-α-induced STAT3 activation and astrogliogenesis. This study generates important data elucidating the role of TNF-α in neurogenesis and may provide insight into new therapeutic strategies for brain inflammation. Public Library of Science 2012-12-07 /pmc/articles/PMC3517586/ /pubmed/23236394 http://dx.doi.org/10.1371/journal.pone.0050783 Text en © 2012 Lan 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
Lan, Xiqian
Chen, Qiang
Wang, Yongxiang
Jia, Beibei
Sun, Lijun
Zheng, Jialin
Peng, Hui
TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor
title TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor
title_full TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor
title_fullStr TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor
title_full_unstemmed TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor
title_short TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor
title_sort tnf-α affects human cortical neural progenitor cell differentiation through the autocrine secretion of leukemia inhibitory factor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517586/
https://www.ncbi.nlm.nih.gov/pubmed/23236394
http://dx.doi.org/10.1371/journal.pone.0050783
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