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.
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.
Xia
M Q
MQ
Alzheimer's Research, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Harvard, MA 02129, USA.
Bacskai
B J
BJ
Knowles
R B
RB
Qin
S X
SX
Hyman
B T
BT
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D058225:Plaque, Amyloid / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D015854:Up-Regulation
C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D020928:Mitogen-Activated Protein Kinases