Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons

Coughlan, Christine M.; McManus, Carrie M.; Sharron, Matthew; Gao, Zhiyong; Murphy, Diane D.; Jaffer, Salman; Choe, Wonkyu; Chen, W; Hesselgesser, Joseph; Gaylord, Harvey R.; Kalyuzhny, Alexander E.; Lee, V.M.-Y; Wolf, Bryan A.; Doms, Robert W.; Kolson, Dennis L.

doi:10.1016/s0306-4522(00)00024-5

Cited by 192 publications

(143 citation statements)

References 44 publications

Supporting

Mentioning

134

Contrasting

Order By: Relevance

“…The hippocampal cultures contain both neurons and glial cells, and both cell types have been shown to express CXCR3, the receptor for CXCL10 (Coughlan et al, 2000;Nelson and Gruol, 2004;Xia et al, 2000). Our immunohistochemical studies showed that in the hippocampal cultures neurons are strongly immunoreactive for CXCR3, whereas the astrocytes are only weakly immunoreactive (Nelson and Gruol, 2004).…”

Section: Neurons and Glial Cells Express The Signal Transduction Pathmentioning

confidence: 51%

“…CXCL10 exerts its biological activity by binding to the G-protein coupled receptor CXCR3, which is expressed on CNS neurons, astrocytes and microglia (Coughlan et al, 2000;Xia et al, 2000). In hippocampal neurons, exogenously applied CXCL10 alters synaptic plasticity (Vlkolinsky et al, 2004), activity-dependent intracellular Ca 2+ signaling and neuronal and synaptic activity (Nelson and Gruol, 2004), suggesting that CXCR3 can regulate pathways that modulate neuronal function.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Bajova

Nelson

Gruol

2008

Journal of Neuroimmunology

View full text Add to dashboard Cite

Signal transduction pathways may be important targets of chemokines during neuroinflammation. In the current study, Western blot analyses show that in rat hippocampal neuronal/glial cell cultures chronic CXCL10 increases the level of protein for ERK1/2 as well as for the transcriptional factors CREB and NF-κB. Bcl-2, an anti-apoptotic protein whose expression can be regulated by a pathway involving ERK1/2, CREB and NF-κB, was also increased in the CXCL10 treated cultures. These results implicate a role for ERK1/2, CREB and NF-κB in effects of CXCL10 on hippocampal cells and suggest that chronic CXCL10 may have a protective role during certain neuroinflammatory conditions.

show abstract

Section: Neurons and Glial Cells Express The Signal Transduction Pathmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Bajova

Nelson

Gruol

2008

Journal of Neuroimmunology

View full text Add to dashboard Cite

show abstract

“…It has previously been reported that CCR2 is expressed on several types of neurons such as human fetal neurons and NT2.N cells (Coughlan et al, 2000) and spinal cord neurons (Gosselin et al, 2005), and that it is constitutively expressed in several regions of the adult rat brain including hippocampus (Banisadr et al, 2005b). The expression of CCR2 has also been reported previously for astrocytes (Andjelkovic et al, 2002;Rezaie et al, 2002).…”

Section: Discussionmentioning

confidence: 71%

The chemokine CCL2 activates p38 mitogen-activated protein kinase pathway in cultured rat hippocampal cells

Cho

Gruol

2008

Journal of Neuroimmunology

View full text Add to dashboard Cite

Emerging evidence indicates that chemokines can regulate both the physiology and biochemistry of CNS neurons and glia. In the current study, Western blot analysis showed that in rat hippocampal neuronal/glial cultures the signal transduction pathway activated by CCL2, a chemokine expressed in the normal brain and at elevated levels during neuroinflammation, involves a G-protein coupled receptor, p38 MAPK as well as its immediate upstream kinase MKK3/6, and the downstream transcription factor CREB. ERK 1/2 and the transcription factors STAT1 and STAT3 do not play a prominent role. CCL2 also altered Ca 2+ influx and synaptic network activity in the hippocampal neurons. These results suggest an important role for p38 MAPK and CREB in hippocampal actions of CCL2.

show abstract

“…In HMCs, the CCR2 receptor also mediates MCP-1-induced ICAM-1 levels [17]. Therefore, HMCs produce a functionally active CCR2 receptor as previously shown both in vitro [8][9][10][11][12] and in vivo [13][14][15]35] in other nonmononuclear cell types.…”

Section: Discussionmentioning

confidence: 76%

“…However, a functionally active CCR2 receptor has been demonstrated in other cell types both in vitro [8][9][10][11][12] and in vivo [13][14][15], suggesting that MCP-1 may have other functional effects beyond monocyte recruitment [16]. Accordingly, we recently reported that in human mesangial cells (HMCs) MCP-1 binding to CCR2 induces intercellular adhesion molecule-1 (ICAM-1) production, leading to enhanced monocyte adhesion [17].…”

Section: Introductionmentioning

confidence: 99%

Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis Diabetic nephropathy is characterised by mesangial extracellular matrix accumulation. Monocyte chemoattractant protein-1 (MCP-1), a chemokine promoting monocyte infiltration, is upregulated in the diabetic glomerulus. We performed in vitro and in vivo studies to examine whether MCP-1 may have prosclerotic actions in the setting of diabetes, presumably via its receptor, chemokine (C-C motif) receptor 2 (CCR2), which has been described in mesangial cells. Methods Human mesangial cells were exposed to recombinant human (rh)-MCP-1 (100 ng/ml) for 12, 24 and 48 h and to rh-MCP-1 (10, 100 and 200 ng/ml) for 24 h. Fibronectin, collagen IV and transforming growth factor, beta 1 (TGF-β1) protein levels were measured by ELISA and pericellular polymeric fibronectin levels by western blotting. The intracellular mechanisms were investigated using specific inhibitors for CCR2, nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase and protein kinase C, and an anti-TGF-β1 blocking antibody. In both non-diabetic and streptozotocin-induced diabetic mice that were deficient or not in MCP-1, glomerular fibronectin accumulation was examined by immunohistochemistry, while cortical Tgf-β1 (also known as Tgfb1) and fibronectin mRNA and protein levels were examined by real-time PCR and western blotting. Results In mesangial cells, MCP-1 binding to CCR2 induced a 2.5-fold increase in fibronectin protein levels at 24 h followed by a rise in pericellular fibronectin, whereas no changes were seen in collagen IV production. MCP-1-induced fibronectin production was TGF-β1-and NF-κB-dependent. In diabetic mice, loss of MCP-1 diminished glomerular fibronectin protein production and both renal cortical Tgf-β1 and fibronectin mRNA and protein levels. Conclusions/interpretation Our in vitro and in vivo findings indicate a role for the MCP-1/CCR2 system in fibronectin deposition in the diabetic glomerulus, providing a new therapeutic target for diabetic nephropathy.

show abstract

Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons

Cited by 192 publications

References 44 publications

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

The chemokine CCL2 activates p38 mitogen-activated protein kinase pathway in cultured rat hippocampal cells

Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells

Contact Info

Product

Resources

About