Interleukin-1β mediates proliferation and differentiation of multipotent neural precursor cells through the activation of SAPK/JNK pathway

Xiaofei Wang, Saili Fu, Yanxia Wang, Panpan Yu, Jianguo Hu, Wenli Gu, Xiao-Ming Xu, Peihua Lu

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Neural precursor cells (NPCs) have been experimentally used to repair the damaged nervous system either by exogenous transplantation or by endogenous activation. In post-injury inflammation, an array of cytokines including interleukin-1β (IL-1β) are released by host as well as invading immune cells and increased markedly. In the present study, we investigated the effects of IL-1β on the survival, proliferation, differentiation and migration of NPCs as well as underlying intracellular signaling pathways. NPCs derived from the E16 rat brain were expanded in neurospheres that were found to express IL-1β, IL-1RI and IL-1RII, but not IL-1α and IL-1ra. IL-1β inhibited the proliferation of NPCs in a dose-dependent manner, an effect that can be reversed by IL-1ra, an antagonist for IL-1 receptor. This inhibitory effect of IL-1β on NPCs proliferation resulted in part from its effect on increased apoptosis of NPCs. Moreover, IL-1ra did not affect NPCs lineage fate but rather inhibited GFAP expression in differentiated astrocytes. We also found that IL-1ra had no effect on the transmigration of NPCs in vitro. Finally, we showed that the effect of IL-1β on NPCs proliferation and differentiation appeared to be mediated by SAPK/JNK, but not ERK, P38MAPK nor NF-κB pathways. These findings collectively suggest that the inflammatory environment following CNS injuries may influence the ability of NPCs to repair the damage.

Original languageEnglish (US)
Pages (from-to)343-354
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume36
Issue number3
DOIs
StatePublished - Nov 2007
Externally publishedYes

Fingerprint

MAP Kinase Signaling System
Interleukin-1
Interleukin 1 Receptor Antagonist Protein
Cell Proliferation
Interleukin-1 Receptors
Wounds and Injuries
Cell Lineage
Astrocytes
Nervous System
Cell Differentiation
Transplantation
Apoptosis
Cytokines
Inflammation
Brain

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Interleukin-1β mediates proliferation and differentiation of multipotent neural precursor cells through the activation of SAPK/JNK pathway. / Wang, Xiaofei; Fu, Saili; Wang, Yanxia; Yu, Panpan; Hu, Jianguo; Gu, Wenli; Xu, Xiao-Ming; Lu, Peihua.

In: Molecular and Cellular Neuroscience, Vol. 36, No. 3, 11.2007, p. 343-354.

Research output: Contribution to journalArticle

Wang, Xiaofei ; Fu, Saili ; Wang, Yanxia ; Yu, Panpan ; Hu, Jianguo ; Gu, Wenli ; Xu, Xiao-Ming ; Lu, Peihua. / Interleukin-1β mediates proliferation and differentiation of multipotent neural precursor cells through the activation of SAPK/JNK pathway. In: Molecular and Cellular Neuroscience. 2007 ; Vol. 36, No. 3. pp. 343-354.
@article{cfc84277c4e44f5c98a17d1918fd1e21,
title = "Interleukin-1β mediates proliferation and differentiation of multipotent neural precursor cells through the activation of SAPK/JNK pathway",
abstract = "Neural precursor cells (NPCs) have been experimentally used to repair the damaged nervous system either by exogenous transplantation or by endogenous activation. In post-injury inflammation, an array of cytokines including interleukin-1β (IL-1β) are released by host as well as invading immune cells and increased markedly. In the present study, we investigated the effects of IL-1β on the survival, proliferation, differentiation and migration of NPCs as well as underlying intracellular signaling pathways. NPCs derived from the E16 rat brain were expanded in neurospheres that were found to express IL-1β, IL-1RI and IL-1RII, but not IL-1α and IL-1ra. IL-1β inhibited the proliferation of NPCs in a dose-dependent manner, an effect that can be reversed by IL-1ra, an antagonist for IL-1 receptor. This inhibitory effect of IL-1β on NPCs proliferation resulted in part from its effect on increased apoptosis of NPCs. Moreover, IL-1ra did not affect NPCs lineage fate but rather inhibited GFAP expression in differentiated astrocytes. We also found that IL-1ra had no effect on the transmigration of NPCs in vitro. Finally, we showed that the effect of IL-1β on NPCs proliferation and differentiation appeared to be mediated by SAPK/JNK, but not ERK, P38MAPK nor NF-κB pathways. These findings collectively suggest that the inflammatory environment following CNS injuries may influence the ability of NPCs to repair the damage.",
author = "Xiaofei Wang and Saili Fu and Yanxia Wang and Panpan Yu and Jianguo Hu and Wenli Gu and Xiao-Ming Xu and Peihua Lu",
year = "2007",
month = "11",
doi = "10.1016/j.mcn.2007.07.005",
language = "English (US)",
volume = "36",
pages = "343--354",
journal = "Molecular and Cellular Neurosciences",
issn = "1044-7431",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Interleukin-1β mediates proliferation and differentiation of multipotent neural precursor cells through the activation of SAPK/JNK pathway

AU - Wang, Xiaofei

AU - Fu, Saili

AU - Wang, Yanxia

AU - Yu, Panpan

AU - Hu, Jianguo

AU - Gu, Wenli

AU - Xu, Xiao-Ming

AU - Lu, Peihua

PY - 2007/11

Y1 - 2007/11

N2 - Neural precursor cells (NPCs) have been experimentally used to repair the damaged nervous system either by exogenous transplantation or by endogenous activation. In post-injury inflammation, an array of cytokines including interleukin-1β (IL-1β) are released by host as well as invading immune cells and increased markedly. In the present study, we investigated the effects of IL-1β on the survival, proliferation, differentiation and migration of NPCs as well as underlying intracellular signaling pathways. NPCs derived from the E16 rat brain were expanded in neurospheres that were found to express IL-1β, IL-1RI and IL-1RII, but not IL-1α and IL-1ra. IL-1β inhibited the proliferation of NPCs in a dose-dependent manner, an effect that can be reversed by IL-1ra, an antagonist for IL-1 receptor. This inhibitory effect of IL-1β on NPCs proliferation resulted in part from its effect on increased apoptosis of NPCs. Moreover, IL-1ra did not affect NPCs lineage fate but rather inhibited GFAP expression in differentiated astrocytes. We also found that IL-1ra had no effect on the transmigration of NPCs in vitro. Finally, we showed that the effect of IL-1β on NPCs proliferation and differentiation appeared to be mediated by SAPK/JNK, but not ERK, P38MAPK nor NF-κB pathways. These findings collectively suggest that the inflammatory environment following CNS injuries may influence the ability of NPCs to repair the damage.

AB - Neural precursor cells (NPCs) have been experimentally used to repair the damaged nervous system either by exogenous transplantation or by endogenous activation. In post-injury inflammation, an array of cytokines including interleukin-1β (IL-1β) are released by host as well as invading immune cells and increased markedly. In the present study, we investigated the effects of IL-1β on the survival, proliferation, differentiation and migration of NPCs as well as underlying intracellular signaling pathways. NPCs derived from the E16 rat brain were expanded in neurospheres that were found to express IL-1β, IL-1RI and IL-1RII, but not IL-1α and IL-1ra. IL-1β inhibited the proliferation of NPCs in a dose-dependent manner, an effect that can be reversed by IL-1ra, an antagonist for IL-1 receptor. This inhibitory effect of IL-1β on NPCs proliferation resulted in part from its effect on increased apoptosis of NPCs. Moreover, IL-1ra did not affect NPCs lineage fate but rather inhibited GFAP expression in differentiated astrocytes. We also found that IL-1ra had no effect on the transmigration of NPCs in vitro. Finally, we showed that the effect of IL-1β on NPCs proliferation and differentiation appeared to be mediated by SAPK/JNK, but not ERK, P38MAPK nor NF-κB pathways. These findings collectively suggest that the inflammatory environment following CNS injuries may influence the ability of NPCs to repair the damage.

UR - http://www.scopus.com/inward/record.url?scp=35448977752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35448977752&partnerID=8YFLogxK

U2 - 10.1016/j.mcn.2007.07.005

DO - 10.1016/j.mcn.2007.07.005

M3 - Article

VL - 36

SP - 343

EP - 354

JO - Molecular and Cellular Neurosciences

JF - Molecular and Cellular Neurosciences

SN - 1044-7431

IS - 3

ER -