Glial and neuronal cells express functional chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor 1.
Chemokines are a family of proteins that chemoattract and activate cells by interacting with specific receptors on the surface of their targets. The chemokine stromal cell-derived factor 1, (SDF1), binds to the seven-transmembrane G protein-coupled CXCR4 receptor and acts to modulate cell migration, differentiation, and proliferation. CXCR4 and SDF1 are reported to be expressed in various tissues including brain. Here we show that SDF1 and CXCR4 are expressed in cultured cortical type I rat astrocytes, cortical neurons, and cerebellar granule cells. In cortical astrocytes, prolonged treatment with lipopolysaccharide induced an increase of SDF1 expression and a down-regulation of CXCR4, whereas treatment with phorbol esters did not affect SDF1 expression and down-modulated CXCR4 receptor expression. We also demonstrated the ability of human SDF1alpha (hSDF1alpha) to increase the intracellular calcium level in cultured astrocytes and cortical neurons, whereas in the same conditions, cerebellar granule cells did not modify their intracellular calcium concentration. Furthermore, in cortical astrocytes, the simultaneous treatment of hSDF1alpha with the HIV-1 capside glycoprotein gp120 inhibits the cyclic AMP formation induced by forskolin treatment.
Bajetto
A
A
Neuroscience Unit, Advanced Biotechnology Centre, Genova, Italy.
Bonavia
R
R
Barbero
S
S
Piccioli
P
P
Costa
A
A
Florio
T
T
Schettini
G
G
D015526:AIDS Dementia Complex / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D002540:Cerebral Cortex / Q000166:cytology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D002522:Chlorocebus aethiops; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D019084:Fluorescent Antibody Technique, Indirect; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000502:physiology; D005786:Gene Expression Regulation; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015290:Second Messenger Systems / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D008024:Ligands; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D019718:Receptors, CXCR4; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000242:Cyclic AMP; D019206:GTP-Binding Protein alpha Subunits, Gi-Go