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

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)24-34
Number of pages11
JournalNeurobiology of Aging
Volume35
Issue number1
DOIs
Publication statusPublished - Jan 2014

    Fingerprint

Keywords

  • Alzheimer's disease
  • Astrocytes
  • CEBPD
  • GSK3β
  • Microglia

ASJC Scopus subject areas

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

Cite this