title: 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.
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.
authors.affiliation: Alzheimer's Research, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Harvard, MA 02129, USA.
authors.forename: M Q
authors.initials: MQ
authors.lastname: Xia
authors.forename: B J
authors.initials: BJ
authors.lastname: Bacskai
authors.forename: R B
authors.initials: RB
authors.lastname: Knowles
authors.forename: S X
authors.initials: SX
authors.lastname: Qin
authors.forename: B T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: 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
chemical_list: 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