CXCR7 is an active component of SDF-1 signalling in astrocytes and Schwann cells

Ödemis, Veysel; Boosmann, Karina; Heinen, André; Küry, Patrick; Engele, Jürgen

doi:10.1242/jcs.062810

Cited by 99 publications

(55 citation statements)

References 58 publications

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“…S3); in particular, stromal cell-derived factor-1 (SDF-1) demonstrates a trend similar to that observed with SC. Recently, it was demonstrated that the SDF-1 receptor, CXCR7, is an active component of SDF-1 signaling in SC [55], suggesting a possible autocrine mechanism. However, further investigation is necessary to identify the precise signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Effect of modulating macrophage phenotype on peripheral nerve repair

et al. 2012

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Peripheral nerve repair across long gaps remains clinically challenging despite progress made with autograft transplantation. While scaffolds that present trophic factors and extracellular matrix molecules have been designed, matching the performance of autograft-induced repair has been challenging. In this study, we explored the effect of cytokine mediated ‘biasing’ of macrophage phenotypes on Schwann cell (SC) migration and axonal regeneration in vitro and in vivo. Macrophage phenotype was successfully modulated by local delivery of either Interferon-gamma (IFN-γ) or Interleukin-4 (IL-4) within polymeric nerve guidance channels, polarizing them toward pro-inflammatory (M1) or pro-healing (M2a and M2c) phenotypes, respectively. The initial polarization of macrophages to M2a and M2c phenotype results in enhanced SC infiltration and substantially faster axonal growth in a critically-sized rat sciatic nerve gap model (15 mm). The ratio of pro-healing to pro-inflammatory population of macrophages (CD206+/CCR7+), defined as regenerative bias, demonstrates a linear relationship with the number of axons at the distal end of the nerve scaffolds. The present results clearly suggest that rather than the extent of macrophage presence, their specific phenotype at the site of injury regulates the regenerative outcomes.

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Section: Discussionmentioning

confidence: 99%

Effect of modulating macrophage phenotype on peripheral nerve repair

et al. 2012

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“…Like MIP-2, CXCL12 can also activate PI-3-K, ERK and cAMP-dependent transcription factor CREB survival pathways in neurons that may afford neuroprotection (Floridi et al, 2003; Lu et al, 2009; Sengupta et al, 2009; Wu et al, 2009). Activation of the chemokine receptor CXCR7 by CXCL12 also activated PI-3-K and ERK pathways that may stabilize the survival of astrocytes when challenged by neurotoxic agents like Aβ (Odemis et al, 2010). Loss of ADAM17 upon Aβ treatment seen in our study is in agreement with observed decreased levels of ADAM17 in AD (Bernstein et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1α, suppress amyloid β-induced neurotoxicity

Raman

Milatovic

Milatović

et al. 2011

Toxicology and Applied Pharmacology

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Alzheimer’s disease (AD) is characterized by a progressive cognitive decline and accumulation of neurotoxic oligomeric peptides amyloid-β (Aβ). Although the molecular events are not entirely known, it has become evident that inflammation, environmental and other risk factors may play a causal, disruptive and/or protective role in the development of AD. The present study investigated the ability of the chemokines, macrophage inflammatory protein-2 (MIP-2) and stromal cell-derived factor-1α (SDF-1α), the respective ligands for chemokine receptors CXCR2 and CXCR4, to suppress Aβ-induced neurotoxicity in vitro and in vivo. Pretreatment with MIP-2 or SDF-1α significantly protected neurons from Aβ-induced dendritic regression and apoptosis in vitro through activation of Akt, ERK1/2 and maintenance of metalloproteinase ADAM17 especially with SDF-1α. Intra-cerebroventricular (ICV) injection of Aβ led to reduction in dendritic length and spine density of pyramidal neurons in the CA1 area of the hippocampus and increased oxidative damage 24 h following the exposure. The Aβ-induced morphometric changes of neurons and increase in biomarkers of oxidative damage, F2-isoprostanes, was significantly inhibited by pretreatment with the chemokines MIP-2 or SDF-1α. Additionally, MIP-2 or SDF-1α was able to suppress the aberrant mislocalization of p21-activated kinase (PAK), one of the proteins involved in the maintenance of dendritic spines. Furthermore, MIP-2 also protected neurons against Aβ neurotoxicity in CXCR2−/− mice, potentially through observed up regulation of CXCR1 mRNA. Understanding the neuroprotective potential of chemokines is crucial in defining the role for their employment during the early stages of neurodegeneration.

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“…Identification of the CXCL12-CXCR4/CXCR7 axis as a novel therapeutic target led to development of several therapeutic approaches [248, 278]. Examples of these are the anti- CXCR4 drug AMD3100 [279], the CXCL12 analog CTCE-9908 [280, 281, 282], the anti-CXCL12 aptamer NOX-A12 [283], the inhibitor of CXCR4 expression chalcone 4 [284], and the CXCR7-specific inhibitors CCX2066 [278, 283], CCX733 [285] and CCX754 [286, 287]. CXCR4 also has been targeted using monoclonal antibodies and small molecule antagonists [288–291].…”

Section: Therapeutic Targetsmentioning

confidence: 99%

A multi-targeted approach to suppress tumor-promoting inflammation

Samadi

Bilsland

Georgakilas

et al. 2015

Seminars in Cancer Biology

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Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes.

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CXCR7 is an active component of SDF-1 signalling in astrocytes and Schwann cells

Cited by 99 publications

References 58 publications

Effect of modulating macrophage phenotype on peripheral nerve repair

Effect of modulating macrophage phenotype on peripheral nerve repair

Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1α, suppress amyloid β-induced neurotoxicity

A multi-targeted approach to suppress tumor-promoting inflammation

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