Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases

Cartier, Laetitia; Hartley, Oliver; Dubois‐Dauphin, Michel; Krause, Karl‐Heinz

doi:10.1016/j.brainresrev.2004.07.021

Cited by 451 publications

(367 citation statements)

References 256 publications

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“…36 CCL3 binds to the CC-chemokine receptors CCR1 and CCR5, which are expressed by all cells within the central nervous system, including microglia. 37 It was suggested that CCR5 activation on microglia might protect again microglial neurotoxicity. 38 Nevertheless, a broad-spectrum chemokine receptor antagonist, blocking in particular CCR5 and CCR1 activity, has been shown to protect the brain against focal cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Tissue Plasminogen Activator Enhances Microglial Cell Recruitment after Stroke in Mice

Lenglet

Montecucco

Coutts

et al. 2014

J Cereb Blood Flow Metab

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The effect of recombinant human tissue plasminogen activator (rtPA) on neuroinflammation after stroke remains largely unknown. Here, we tested the effect of rtPA on expression of cellular adhesion molecules, chemokines, and cytokines, and compared those with levels of inflammatory cell recruitment, brain injury, and mortality over 3 days after transient middle cerebral artery occlusion (MCAO) in mice. Mortality was dramatically increased after rtPA treatment compared with saline treatment during the first day of reperfusion. Among the animals that survived, rtPA significantly increased CCL3 expression, microglia recruitment, and cerebral infarction 6 hours after MCAO. In contrast, the extent of neutrophils and macrophages infiltration in the brain was similar in both saline-and rtPA-treated animals. Recombinant human tissue plasminogen activator induced Il1b and Tnf expression, 6 and 72 hours after MCAO, respectively, and dramatically reduced interleukin 6 (IL-6) level 24 hours after reperfusion. A dose response study confirmed the effect of rtPA on CCL3 and Il1b expressions. The effect was similar at the doses of 1 and 10 mg/kg. In conclusion, we report for the first time that rtPA amplified microglia recruitment early after stroke in association with a rapid CCL3 production. This early response may take part in the higher susceptibility of rtPA-treated animals to reperfusion injury.

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Section: Discussionmentioning

confidence: 99%

Recombinant Tissue Plasminogen Activator Enhances Microglial Cell Recruitment after Stroke in Mice

Lenglet

Montecucco

Coutts

et al. 2014

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

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“…Chemokines have been reported to produce cellular actions by activating a variety of signal transduction pathways (Cartier et al, 2005). Our previous studies showing that acute exposure to CXCL10 alters neuronal excitability and synaptic transmission in hippocampal cultures (Nelson and Gruol, 2004) provides evidence for the expression of a CXCL10 signaling pathway in the hippocampal cells.…”

Section: Chronic Cxcl10 Increases the Level Of Activated Erk1/2mentioning

confidence: 94%

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

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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.

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“…G proteins are then activated, driving dissociation of their heterotrimers into ␣ and ␤␥ subunits. Next, various signaling cascade effectors are activated, including phospholipase C (PLC), MAP kinases, or phosphatidyl inositol-3OH kinase (PI-3K), 11,12 which leads to functional outcomes induced by chemokine receptor signaling (FIG. 3).…”

Section: Chemokine Receptorsmentioning

confidence: 99%

“…Chemokines-the term is a contraction of chemotactic cytokines-comprise a large family of small (8)(9)(10)(11)(12)(13)(14) basic proteins that display a wide variety of biological and pathological functions. In vitro, the signature assay for chemokines involves stimulation of leukocyte chemotaxis in a concentration-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

Chemokines and Chemokine Receptors in Neurological Disease: Raise, Retain, or Reduce?

Savarin-Vuaillat¹,

Ransohoff²

2007

Neurotherapeutics

156

126

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Summary:Chemokines and chemokine receptors comprise a large number of molecules implicated in a wide range of physiological and pathological functions. Numerous studies have demonstrated the roles of chemokines and chemokine receptors: 1) during development, by regulating hematopoiesis, cardiogenesis, and vascular and cerebellar development; 2) during tumor biology, by controlling cell proliferation, angiogenesis, and metastasis; and 3), especially during leukocyte migration, by acting on firm adhesion, locomotion, diapedesis, and chemotaxis. This review focuses on chemokine and chemokine receptor involvement in diverse neurological diseases and their therapeutic potentials. Because of its induction or upregulation during CNS pathologies, members of the chemokine system can be used as biological markers. CXCR4 and CXCL12, by the correlation between their expression and the glioblastoma tumor progression, could be a marker to grade this type of CNS tumor. CCR1, by virtue of specific expression in A␤ plaques, may be a marker for Alzheimer pathology. Downregulation of CCL2 in cerebrospinal fluid may be a candidate to characterize multiple sclerosis (MS), but needs additional investigation. Moreover, chemokines and chemokine receptors represent interesting therapeutic targets. Using chemokine receptor antagonists, several studies provided exciting findings for potential neurological disease treatment. Chemokine receptor antagonists reduce disease severity in animal models of MS. In glioblastoma, a CXCR4 antagonist (AMD3100) showed an inhibition of tumor growth. Inhibition of chemokine receptor signaling is not the only therapeutic strategy: for example, CXCR4 -CXCL12 has anti-inflammatory properties and CX3CL1-CX3CR1 controls neurotoxicity. Thus, chemokine biology suggests several approaches for treating neurological disease.

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Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases

Cited by 451 publications

References 256 publications

Recombinant Tissue Plasminogen Activator Enhances Microglial Cell Recruitment after Stroke in Mice

Recombinant Tissue Plasminogen Activator Enhances Microglial Cell Recruitment after Stroke in Mice

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

Chemokines and Chemokine Receptors in Neurological Disease: Raise, Retain, or Reduce?

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