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

Xiqian Lan, Qiang Chen, Yongxiang Wang, Beibei Jia, Lijun Sun, Jialin C Zheng, Hui Peng, Colin Combs

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere50783
JournalPloS one
Volume7
Issue number12
DOIs
StatePublished - Dec 7 2012

Fingerprint

Leukemia Inhibitory Factor
cell differentiation
tumor necrosis factor-alpha
stem cells
Cell Differentiation
Stem Cells
Tumor Necrosis Factor-alpha
secretion
STAT3 Transcription Factor
neurogenesis
Neurogenesis
interleukin-6
Transcriptional Activation
Interleukin-6
Chemical activation
leukemia inhibitory factor
Brain
cytokines
Cytokines
Phosphorylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

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 C; Peng, Hui; Combs, Colin.

In: PloS one, Vol. 7, No. 12, e50783, 07.12.2012.

Research output: Contribution to journalArticle

Lan, Xiqian ; Chen, Qiang ; Wang, Yongxiang ; Jia, Beibei ; Sun, Lijun ; Zheng, Jialin C ; Peng, Hui ; Combs, Colin. / TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor. In: PloS one. 2012 ; Vol. 7, No. 12.
@article{8f402eee57d4440cb7ff90508539a65c,
title = "TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor",
abstract = "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.",
author = "Xiqian Lan and Qiang Chen and Yongxiang Wang and Beibei Jia and Lijun Sun and Zheng, {Jialin C} and Hui Peng and Colin Combs",
year = "2012",
month = "12",
day = "7",
doi = "10.1371/journal.pone.0050783",
language = "English (US)",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - TNF-α Affects Human Cortical Neural Progenitor Cell Differentiation through the Autocrine Secretion of Leukemia Inhibitory Factor

AU - Lan, Xiqian

AU - Chen, Qiang

AU - Wang, Yongxiang

AU - Jia, Beibei

AU - Sun, Lijun

AU - Zheng, Jialin C

AU - Peng, Hui

AU - Combs, Colin

PY - 2012/12/7

Y1 - 2012/12/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84870877683&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870877683&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0050783

DO - 10.1371/journal.pone.0050783

M3 - Article

C2 - 23236394

AN - SCOPUS:84870877683

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e50783

ER -