The chemokine receptor CXCR2 is differentially regulated on glial cells <i>in vivo</i> but is not required for successful remyelination after cuprizone‐induced demyelination

Lindner, Maren; Trebst, Corinna; Heine, Sandra; Skripuletz, Thomas; Koutsoudaki, Paraskevi N.; Stangel, Martin

doi:10.1002/glia.20682

Cited by 35 publications

(26 citation statements)

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“…The latter chemokine is released by reactive astrocytes and is known to halt OPC differentiation in vivo (Tsai et al 2002). However, this concept has not been supported by cuprizone-induced demyelination in CXCR2-deficient mice, as no impaired OPC recruitment has been observed (Lindner et al 2008). The controversial role of CXCL1/CXCR2 remains to be investigated further.…”

Section: Cxcl1-cxcl8: Cxcr2 Ligandsmentioning

confidence: 97%

Chemokines in CNS injury and repair

2012

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Recruitment of inflammatory cells is known to drive the secondary damage cascades that are common to injuries of the central nervous system (CNS). Cell activation and infiltration to the injury site is orchestrated by changes in the expression of chemokines, the chemoattractive cytokines. Reducing the numbers of recruited inflammatory cells by the blocking of the action of chemokines has turned out be a promising approach to diminish neuroinflammation and to improve tissue preservation and neovascularization. In addition, several chemokines have been shown to be essential for stem/progenitor cell attraction, their survival, differentiation and cytokine production. Thus, chemokines might indirectly participate in remyelination, neovascularization and neuroprotection, which are important prerequisites for CNS repair after trauma. Moreover, CXCL12 promotes neurite outgrowth in the presence of growth inhibitory CNS myelin and enhances axonal sprouting after spinal cord injury (SCI). Here, we review current knowledge about the exciting functions of chemokines in CNS trauma, including SCI, traumatic brain injury and stroke. We identify common principles of chemokine action and discuss the potentials and challenges of therapeutic interventions with chemokines.

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Section: Cxcl1-cxcl8: Cxcr2 Ligandsmentioning

confidence: 97%

Chemokines in CNS injury and repair

2012

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“…Histology for Luxol-fast blue periodic acid-Schiff base (LFB-PAS) and immunohistochemistry were performed as previously described [20]. Paraffin embedded sections were de-waxed, rehydrated, and microwaved for 5 min in 10 mM citrate buffer (pH 6.0).…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Beneficial Effects of Minocycline on Cuprizone Induced Cortical Demyelination

et al. 2010

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In this study, we investigated the potential of minocycline to influence cuprizone induced demyelination in the grey and white matter. To induce demyelination C57BL/6 mice were fed with cuprizone for up to 6 weeks and were analysed at different timepoints (week 0, 4, 5, 6). Mice treated with minocycline had less demyelination of the cortex and corpus callosum compared with sham treated animals. In the cortex decreased numbers of activated and proliferating microglia were found after 6 weeks of cuprizone feeding, while there were no significant effects for microglial infiltration of the corpus callosum. In addition to the beneficial effects on demyelination, minocycline prevented from motor coordination disturbance as shown in the beam walking test. For astrogliosis and the numbers of OPC and oligodendrocytes no treatment effects were found. In summary, minocycline treatment diminished the course of demyelination in the grey and white matter and prevented disturbances in motor coordination.

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“…In addition, it was shown that CXCR2 activation might directly contribute to motor neuron degeneration [61]. Since the expression of CXCR2 has also been detected in neurons, astrocytes and microglia [62][63][64], more work is required to understand the role of CXCR2 in the CNS both in normal and disease conditions.…”

Section: Nonhematopoietic Cells and Cells Of The Central Nervous Systemmentioning

confidence: 99%

Low Molecular Weight CXCR2 Antagonists as Promising Therapeutics

Mihara¹,

Wijkmans²

2010

Methods and Principles in Medicinal Chemistry

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The chemokine receptor CXCR2 recognizes endogenous chemokines that possess a N-terminal Glu-Leu-Arg (ELR) þ amino acid sequence immediately adjacent to their CXC motif. CXCR2 and the closely related receptor CXCR1 are expressed on the cellular surface of leukocytes, notably neutrophils, endothelial cells and a range of other cell types throughout the human body. It has been firmly established now that CXCR2 plays a critical role in the development of numerous inflammatory disorders, wound healing and tumor progression [1-5]. As classically defined for chemokine receptors, CXCR2 mediates cell migration but has also been recognized as a key angiogenic factor [6,7]. These multifunctional roles have drawn increased attention to CXCR2 as a potentially successful drug target for therapeutic intervention in a range of diseases. The first half of this chapter summarizes the biological role of CXCR2 and its involvement, particularly in inflammatory disorders, in order to illuminate the potential clinical impact and relevance of CXCR2 blocking strategies. A review of all currently known low molecular weight (LMW) CXCR2 antagonists is addressed in the second half of this chapter. CXCR2 Ligands and Signal TransductionCXCR2, which shows 78% overall amino acid identity with CXCR1, was first cloned in 1991 out of human promyelocytic leukemia HL60 cells [8]. Subsequent research demonstrated that CXCR2 is the cognate receptor for at least seven structurally related (ELR) þ chemokines, which are growth-related protein (Gro)-a, -b and -c (CXCL1-CXCL3), epithelium-derived neutrophil attractant-78 (ENA-78; CXCL5), granulocyte chemotactic protein-2 (GCP-2; CXCL6), neutrophil-activating peptide-2 (NAP-2; CXCL7) and interleukin-8 (IL-8; CXCL8) [9, 10]. In contrast,

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The chemokine receptor CXCR2 is differentially regulated on glial cells in vivo but is not required for successful remyelination after cuprizone‐induced demyelination

Cited by 35 publications

References 50 publications

Chemokines in CNS injury and repair

Chemokines in CNS injury and repair

Beneficial Effects of Minocycline on Cuprizone Induced Cortical Demyelination

Low Molecular Weight CXCR2 Antagonists as Promising Therapeutics

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