Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes: in vitro ERK1/2 activation and role in Alzheimer's disease

J Neuroimmunol. 2000 Aug 1;108(1-2):227-35. doi: 10.1016/s0165-5728(00)00285-x.

Abstract

Inflammatory mediators have been implicated in the pathophysiology of neurodegenerative diseases. Here we report the presence of the chemokine receptor CXCR3 and its ligand, IP-10, in normal and Alzheimer's disease (AD) brains. CXCR3 was detected constitutively on neurons and neuronal processes in various cortical and subcortical regions; IP-10 was observed in a subpopulation of astrocytes in normal brain, and was markedly elevated in astrocytes in AD brains. Many IP-10(+) astrocytes were associated with senile plaques and had an apparently coordinated upregulation of MIP-1beta. Moreover, we showed that CXCR3 ligands, IP-10 and Mig, were able to activate ERK1/2 pathway in mouse cortical neurons, suggesting a novel mechanism of neuronal-glial interaction.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Animals
  • Astrocytes / cytology
  • Astrocytes / enzymology
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Chemokine CCL4
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC / metabolism*
  • Chemokines, CXC / pharmacology
  • Enzyme Activation / drug effects
  • Female
  • Gene Expression Profiling
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Ligands
  • MAP Kinase Signaling System / drug effects
  • Macrophage Inflammatory Proteins / metabolism
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neurons / cytology
  • Neurons / enzymology
  • Neurons / metabolism*
  • Neurons / pathology
  • Phosphorylation / drug effects
  • Plaque, Amyloid / enzymology
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Receptors, CXCR3
  • Receptors, Chemokine / metabolism*
  • Up-Regulation

Substances

  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CCL4
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC
  • Cxcr3 protein, mouse
  • Glial Fibrillary Acidic Protein
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Macrophage Inflammatory Proteins
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Mitogen-Activated Protein Kinases