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Fractalkine and fractalkine receptors in human neurons and glial cells.

Authors
Hatori, K; Nagai, A; Heisel, R; Ryu, JK; Kim, SU
Citation
Journal of neuroscience research, 69(3):418-426, 2002
Journal Title
Journal of neuroscience research
ISSN
0360-40121097-4547
Abstract
Fractalkine has been identified as a novel chemokine that exhibits cell adhesion and chemoattractive properties in the central nervous system (CNS), and the fractalkine receptors, CX3CR1, are also expressed in the CNS. In the present study, the expression of fractalkine and fractalkine receptors was investigated in enriched populations of human CNS neurons, astrocytes, and microglia. In addition, the regulatory role played by protein kinase C (PKC) in fractalkine secretion in neurons was determined in A1 human hybrid neuronal cell line produced between a human cerebral neuron and a human neuroblastoma cell. Human neurons and astrocytes expressed fractalkine mRNA as determined by the revserse transcriptase-polymerase chain reaction (RT-PCR) analysis, while human microglia preparation did not express the fractalkine message. Human neurons and microglia expressed CX3CR1 mRNA, but astrocytes did not. These results suggest that fractalkine secreted by CNS neurons and astrocytes produce biological effects in neurons and microglia. Although phorbol ester did not change the expression of fractalkine mRNA level in A1 hybrid neurons, it did upregulate fractalkine secretion over unstimulated controls. This upregulation of fractalkine production was suppressed by the treatment with Ro32-0432, a PKC inhibitor. These results indicate that intracellular signals transduced by PKC play an important role in the regulation of soluble fractalkine at the post-transcriptional level in human neurons. As for the biological function of fractalkine, extracellularly applied fractalkine increased the number of bromodeoxyuridine-labeled microglia 3-fold over the untreated controls, indicating fractalkine induces proliferation of human microglia. These observations suggest that fractalkine released by injured neurons could induce proliferation, activation and/or migration of microglia at the injured brain sites.
MeSH terms
Astrocytes/*metabolismCell Culture TechniquesChemokine CX3CL1Chemokines, CX3C/biosynthesis/*metabolismEnzyme ActivationEnzyme Inhibitors/pharmacologyHumansImmunoblottingImmunohistochemistryIndoles/pharmacologyMembrane Proteins/biosynthesis/*metabolismMicroglia/*metabolismNeurons/*metabolismProtein Kinase C/antagonists & inhibitors/metabolismPyrroles/pharmacologyReceptors, Cytokine/*metabolismReceptors, HIV/*metabolismReverse Transcriptase Polymerase Chain ReactionSignal Transduction
DOI
10.1002/jnr.10304
PMID
12125082
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
김, 승업
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