Glial and Neuronal Cells Express Functional Chemokine Receptor CXCR4 and Its Natural Ligand Stromal Cell‐Derived Factor 1

Abstract

Abstract: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 seventransmembrane 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 SDF1␣ (hSDF1␣) 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 hSDF1␣ with the HIV-1 capside glycoprotein gp120 inhibits the cyclic AMP formation induced by forskolin treatment.

Intrathecal HIV-1 Envelope Glycoprotein gp120 Induces Enhanced Pain States Mediated by Spinal Cord Proinflammatory Cytokines

“…Third, gp120 can activate chemokine receptor subtypes on astrocytes and microglia (Popik et al, 1998;Kaul and Lipton, 1999;Klein et al, 1999). This causes G-protein-linked increases in intracellular calcium (Madani et al, 1998;Bajetto et al, 1999). Together, these lines of evidence provide support that rapid NO production would be expected after intrathecal gp120.…”

SDF1α/CXCR4 Signaling, via ERKs and the Transcription Factor Egr1, Induces Expression of a 67-kDa Form of Glutamic Acid Decarboxylase in Embryonic Hippocampal Neurons

“…Previous cell culture studies have provided evidence that signals from glial cells influence development of the GABAergic phenotype of hippocampal neurons during early postnatal development (52). Although the identity of the glial cell-derived factor is unknown, SDF1␣ is one possibility as it is known to be produced by astrocytes (53,54).…”

“…In the adult brain, both neurons and astrocytes express SDF1␣ (53), and the SDF1␣-CXCR4 pathway is therefore poised to regulate development of the GABAergic phenotype during adult hippocampal neurogenesis and the synaptic integration of newly generated neurons. Because perturbations in GABAergic neurons are associated with several different neurological disorders that affect the hippocampus, a possible role for altered SDF1␣/CXCR4/ERK/Egr1 in the GABAergic abnormalities should be considered.…”

Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells

“…To support this all TCSC express CXCR4 receptor on their surface and follow an SDF-1 gradient. 34,38,[50][51][52][53][54][55] Thus the SDF-1-CXCR4 axis alone or in combination with other chemoattractants plays a crucial role in accumulation of TCSC in developing BM. These cells find in BM a permissive environment to survive, and what we believe may play an underappreciated role as a reserve pool of stem cells for organ/tissue regeneration during postnatal life ( Figure 1).…”