Glycogen synthase kinase-3β-mediated CCAAT/enhancer-binding protein delta phosphorylation in astrocytes promot es migration and activation of microglia/macrophages

Chiung Yuan Ko, Wen Ling Wang, Shao Ming Wang, Yu Yi Chu, Wen Chang Chang, Ju-Ming Wang

研究成果: Article

16 引文 (Scopus)

摘要

Alzheimer's disease is neuropathologically characterized by the accumulation of amyloid-β protein into senile plaques that are sites of chronic inflammation involving reactive microglia, astrocytes, and proinflammatory molecules, such as interleukin-1β and tumor necrosis factor-α. The human CCAAT/enhancer-binding protein (CEBP) delta (CEBPD) is known to be induced in many inflammation-related diseases. In Alzheimer's disease, this protein is responsive to amyloid-β and proinflammatory cytokines in astrocytes. However, the functional role of CEBPD in astrocytes remains largely unclear. In this study, we show that CEBPD is upregulated by interleukin-1β through the mitogen-activated protein kinase p38 (MAPKp38) signaling pathway and phosphorylated by glycogen synthase kinase (GSK)-3β at Ser167 in astrocytes. CEBPD in astrocytes is associated with microglia activation and migration in amyloid precursor protein transgenic mice (AppTg) mice. We further identified that the monocyte chemotactic protein-1, a chemoattractive factor, and migration factors matrix metalloproteinase-1 and -3 are responsive to GSK3β-mediated CEBPD Ser167 phosphorylation. Our results revealed the novel regulation of LiCl on astrocytes and that GSK3β-mediated CEBPD phosphorylation in astrocytes plays an important role in the activation of microglia.

原文English
頁(從 - 到)24-34
頁數11
期刊Neurobiology of Aging
35
發行號1
DOIs
出版狀態Published - 2014 一月 1

指紋

CCAAT-Enhancer-Binding Protein-delta
Glycogen Synthase Kinase 3
Macrophage Activation
Microglia
Astrocytes
Phosphorylation
Interleukin-1
Alzheimer Disease
Inflammation
Amyloidogenic Proteins
Matrix Metalloproteinase 3
Matrix Metalloproteinase 1
Amyloid beta-Protein Precursor
Chemokine CCL2
Amyloid Plaques
p38 Mitogen-Activated Protein Kinases
Amyloid
Transgenic Mice
Tumor Necrosis Factor-alpha
Cytokines

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

引用此文

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title = "Glycogen synthase kinase-3β-mediated CCAAT/enhancer-binding protein delta phosphorylation in astrocytes promot es migration and activation of microglia/macrophages",
abstract = "Alzheimer's disease is neuropathologically characterized by the accumulation of amyloid-β protein into senile plaques that are sites of chronic inflammation involving reactive microglia, astrocytes, and proinflammatory molecules, such as interleukin-1β and tumor necrosis factor-α. The human CCAAT/enhancer-binding protein (CEBP) delta (CEBPD) is known to be induced in many inflammation-related diseases. In Alzheimer's disease, this protein is responsive to amyloid-β and proinflammatory cytokines in astrocytes. However, the functional role of CEBPD in astrocytes remains largely unclear. In this study, we show that CEBPD is upregulated by interleukin-1β through the mitogen-activated protein kinase p38 (MAPKp38) signaling pathway and phosphorylated by glycogen synthase kinase (GSK)-3β at Ser167 in astrocytes. CEBPD in astrocytes is associated with microglia activation and migration in amyloid precursor protein transgenic mice (AppTg) mice. We further identified that the monocyte chemotactic protein-1, a chemoattractive factor, and migration factors matrix metalloproteinase-1 and -3 are responsive to GSK3β-mediated CEBPD Ser167 phosphorylation. Our results revealed the novel regulation of LiCl on astrocytes and that GSK3β-mediated CEBPD phosphorylation in astrocytes plays an important role in the activation of microglia.",
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Glycogen synthase kinase-3β-mediated CCAAT/enhancer-binding protein delta phosphorylation in astrocytes promot es migration and activation of microglia/macrophages. / Ko, Chiung Yuan; Wang, Wen Ling; Wang, Shao Ming; Chu, Yu Yi; Chang, Wen Chang; Wang, Ju-Ming.

於: Neurobiology of Aging, 卷 35, 編號 1, 01.01.2014, p. 24-34.

研究成果: Article

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AU - Chu, Yu Yi

AU - Chang, Wen Chang

AU - Wang, Ju-Ming

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AB - Alzheimer's disease is neuropathologically characterized by the accumulation of amyloid-β protein into senile plaques that are sites of chronic inflammation involving reactive microglia, astrocytes, and proinflammatory molecules, such as interleukin-1β and tumor necrosis factor-α. The human CCAAT/enhancer-binding protein (CEBP) delta (CEBPD) is known to be induced in many inflammation-related diseases. In Alzheimer's disease, this protein is responsive to amyloid-β and proinflammatory cytokines in astrocytes. However, the functional role of CEBPD in astrocytes remains largely unclear. In this study, we show that CEBPD is upregulated by interleukin-1β through the mitogen-activated protein kinase p38 (MAPKp38) signaling pathway and phosphorylated by glycogen synthase kinase (GSK)-3β at Ser167 in astrocytes. CEBPD in astrocytes is associated with microglia activation and migration in amyloid precursor protein transgenic mice (AppTg) mice. We further identified that the monocyte chemotactic protein-1, a chemoattractive factor, and migration factors matrix metalloproteinase-1 and -3 are responsive to GSK3β-mediated CEBPD Ser167 phosphorylation. Our results revealed the novel regulation of LiCl on astrocytes and that GSK3β-mediated CEBPD phosphorylation in astrocytes plays an important role in the activation of microglia.

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