Expression of stromal cell-derived factor-1 and CXCR4 chemokine receptor mRNAs in cultured rat glial and neuronal cells

Ohtani, Yoshikazu; Minami, Masabumi; Kawaguchi, Nami; Nishiyori, Atsushi; Yamamoto, Junki; Takami, Shinya; Satoh, Masamichi

doi:10.1016/s0304-3940(98)00425-x

Cited by 127 publications

(34 citation statements)

References 16 publications

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“…. Under normal conditions, the regulation of SDF-1-dependent chemotaxis by CXCR4 cell surface expression levels might be essential to prevent aberrant cell migration in response to SDF-1, a chemokine constitutively expressed in all organs yet examined, including the brain (5,15,22,(42)(43)(44). In support of this notion, we observed that cultured cortical astroglia chemotactically responded to MIP-1␣ without prior manipulations of cell surface receptor expression levels.…”

Section: Discussionsupporting

confidence: 58%

“…CXCR4 transcripts are abundantly present in hematopoietic cells and have been detected also in non-hematopoietic organs such as lung, heart, and brain (11,12). In the brain, CXCR4 is constitutively expressed by various neural cell types, including neurons, microglia, and astrocytes (13)(14)(15). Recently, great attention was attracted by the capability of CXCR4 to mediate neuronal cell death upon binding of the HIV envelope protein, gp120, a process believed to underlie HIV dementia (16,17).…”

mentioning

confidence: 99%

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Interleukin-6 and cAMP Induce Stromal Cell-derived Factor-1 Chemotaxis in Astroglia by Up-regulating CXCR4 Cell Surface Expression

Ödemis

Moepps

Gierschik

et al. 2002

Journal of Biological Chemistry

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The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 control the migration of neurons and microglial cells in the central nervous system. Although functional CXCR4 is also expressed by astroglia, recent studies have failed to observe a chemotactic response of these cells to SDF-1. Here, we demonstrate that SDF-1-dependent chemotaxis can be induced by treating cultured cortical astroglia with either dibutyryl cyclic AMP (dbcAMP; 10 ؊4 M) or interleukin-6 (IL-6; 10 ng/ml). Flow cytometric analysis revealed that both the dbcAMP-and IL-6-induced onset of SDF-1-dependent chemotaxis of astroglia are due to the increased cell surface expression of CXCR4. In addition, dbcAMP and IL-6 also increased CXCR4 transcript levels, further suggesting that both treatments primarily affect CXCR4 surface expression in astroglia by stimulation of gene expression. Moreover, unlike the case with IL-6 and dbcAMP, which allowed for an optimal chemotactic response to SDF-1 only after 48 h, a similar chemotactic response, associated with an increase in CXCR4 cell surface expression, already occurred after 24 h when astroglial cultures were maintained with medium conditioned by IL-6-or dbcAMP-pretreated astrocytes, indicating that the stimulatory effects of IL-6 and cAMP on CXCR4 cell surface expression involve a secondary mechanism. The findings that elevated extracellular levels of IL-6 or factors positively coupled to cAMP result in increased CXCR4 cell surface expression levels and subsequent SDF-1-dependent chemotaxis in central nervous system astrocytes point to a crucial role of this chemokine during reactive gliosis and human immunodeficiency virus-mediated dementia.

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Section: Discussionsupporting

confidence: 58%

mentioning

confidence: 99%

Interleukin-6 and cAMP Induce Stromal Cell-derived Factor-1 Chemotaxis in Astroglia by Up-regulating CXCR4 Cell Surface Expression

Ödemis

Moepps

Gierschik

et al. 2002

Journal of Biological Chemistry

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“…Not only are opioid receptors widely expressed in the central nervous system, but there are recent reports showing that CXCR2, CXCR4, CCR1, CCR4, CCR5, CCR9, and CX 3 CR1 are also broadly expressed in the brain, including on neurons in the hippocampus, regions of the cerebral cortex, amygdala, thalamus, and basal ganglia (27,28,32). First, CXCR4 is particularly well expressed in the brain and has been detected on neurons, glial cells, astrocytes, microglial cells, endothelial cells, and blood-derived leukocytes (33)(34)(35)(36)(37)(38). In contrast, CCR5 is less widely distributed, and more weakly expressed, by neurons in the brain (28,32,39).…”

Section: Discussionmentioning

confidence: 99%

Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain

Szabó

Chen²,

Li³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

231

199

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The chemokines use G protein-coupled receptors to regulate the migratory and proadhesive responses of leukocytes. Based on observations that G protein-coupled receptors undergo heterologous desensitization, we have examined the ability of chemokines to also influence the perception of pain by cross-desensitizing opioid G protein-coupled receptors function in vitro and in vivo. We find that the chemotactic activities of both -and ␦-opioid receptors are desensitized following activation of the chemokine receptors CCR5, CCR2, CCR7, and CXCR4 but not of the CXCR1 or CXCR2 receptors. Furthermore, we also find that pretreatment with RAN-TES͞CCL5, the ligand for CCR1, and CCR5 or SDF-1␣͞CXCL12, the ligand for CXCR4, followed by opioid administration into the periaqueductal gray matter of the brain results in an increased rat tail flick response to a painful stimulus. Because chemokine administration into the periaqueductal gray matter inhibits opioidinduced analgesia, we propose that the activation of proinflammatory chemokine receptors down-regulates the analgesic functions of opioid receptors, and this enhances the perception of pain at inflammatory sites. O pioid and chemokine receptors are members of the G i protein-linked seven-transmembrane receptor family. These receptors, as well as the chemokine and endogenous opioid peptide ligands, are widely distributed in brain tissue and the periphery. Chemokines have been classified into four families: C, CC, CXC, and CX 3 C based on the position of conserved cysteines, and they interact with receptors designated CR1, CCR1-11, CXCR1-5, or CX 3 CR1, respectively (1). Three classes of receptors have been identified for the opioids, designated , , and ␦, and each of the opioid receptor genes expressed in brain tissue and immune cells has been cloned and sequenced (2-7).The -, -, and ␦-opioids are known to have inhibitory effects on both antibody and cellular immune responses (8, 9), natural killer cell activity (10), cytokine expression (11-13), and phagocytic activity (14), which may account for the decreased resistance to infections caused by morphine and heroin administration. Furthermore, pretreatment with opioids, including morphine, heroin, met-enkephalin, the selective -agonist ]enkephalin (DPDPE), leads to the inhibition of the chemotactic response of leukocytes to complement-derived chemotactic factors (15) and to the chemokines macrophage inflammatory protein (MIP-1␣)͞CCL3, regulated on activation normal T cell expressed and secreted (RANTES͞CCL5), monocyte chemotactic protein-1 (MCP-1)͞ CCL2, and IL-8͞CXCL8 (16). The latter results suggest that the activation of the -and ␦-opioid receptors leads to the desensitization of the CC chemokine receptor 2 (CCR2) and CXC chemokine receptors CXCR1 and CXCR2. In fact, the latter two receptors are phosphorylated by prior administration of opioids. Moreover, the inhibition of CCL3 and CCL5 responses following opioid pretreatment is consistent with the desensitization of either CCR1 or CCR5, or both. This receptor crosstalk r...

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“…Because SDF-1 is a secreted product, we measured the cell-conditioned medium for the amount of this protein. Non-transformed astrocytes were also used, as these are known sources of SDF-1 (27). Fig.…”

Section: Expression Of Chemokine Receptors By Glioma Cell Lines-mentioning

confidence: 99%

CXCR4 Is a Major Chemokine Receptor on Glioma Cells and Mediates Their Survival

Zhou¹,

Larsen²,

Hao³

et al. 2002

Journal of Biological Chemistry

347

283

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Chemokines were described originally in the context of providing migrational cues for leukocytes. They are now known to have broader activities, including those that favor tumor growth. We addressed whether and which chemokines may be important promoters of the growth of the incurable brain neoplasm, malignant gliomas. Analyses of 16 human glioma lines for the expression of chemokine receptors belonging to the CXCR and CCR series revealed low to negligible levels of all receptors, with the exception of CXCR4 that was expressed by 13 of 16 lines. All six resected human glioma specimens showed similarly high CXCR4 expression. The CXCR4 on glioma lines is a signaling receptor in that its agonist, stromal cell-derived factor-1 (SDF-1; CXCL12), produced rapid phosphorylation of mitogen-activated protein kinases. Furthermore, SDF-1 induced the phosphorylation of Akt (protein kinase B), a kinase associated with survival, and prevented the apoptosis of glioma cells when serum was withdrawn from the culture medium. SDF-1 also mediated glioma chemotaxis, in accordance with this better known role of chemokines. We conclude that glioma cells express a predominant chemokine receptor, CXCR4, and that this functions to regulate survival in part through activating pathways such as Akt.

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Expression of stromal cell-derived factor-1 and CXCR4 chemokine receptor mRNAs in cultured rat glial and neuronal cells

Cited by 127 publications

References 16 publications

Interleukin-6 and cAMP Induce Stromal Cell-derived Factor-1 Chemotaxis in Astroglia by Up-regulating CXCR4 Cell Surface Expression

Interleukin-6 and cAMP Induce Stromal Cell-derived Factor-1 Chemotaxis in Astroglia by Up-regulating CXCR4 Cell Surface Expression

Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain

CXCR4 Is a Major Chemokine Receptor on Glioma Cells and Mediates Their Survival

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