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Cell biology and clinical promise of G-CSF: immunomodulation and neuroprotection.

Xiao BG, Lu CZ, Link H - J. Cell. Mol. Med. (2007 Nov-Dec)

Bottom Line: G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis.Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration.Our understanding of these novel sites of action of G-CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G-CSF from basic experiments to clinical patients.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. bgxiao@shmu.edu.cn

ABSTRACT
In the light of the enthusiasm to use of recombinant human granulocyte colony-stimulating factor (G-CSF) for immunomodulation and neuroprotection, it should be remembered that the current knowledge is based on a century of laborious research. G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis. Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration. Here, we describe the immunomodulation and the neuroprotection that can be achieved with G-CSF, and summarize possible mechanisms of G-CSF as a potential therapeutic agent in autoimmune diseases and neurological disorders. Our understanding of these novel sites of action of G-CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G-CSF from basic experiments to clinical patients.

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Possible mechanisms for neuroprotection of G-CSF in cerebral ischemia and neurodegeneration. G-CSF provokes multiple intracellular signal transductions including Jak/Stat, ERK and PI3K/Akt in neuroprotection. (1) Anti-apoptosis: G-CSF mediates antiapoptotic pathway through ERK or/and JAK/Stat signalling activation and subsequent upregulation of bcl-2 and inhibition of caspase- 3; (2) Neuronal differentiation: Stat regulates VEGF expression, or G-CSF activates endothelial cells to release BDNF.VEGF, BDNF and activated PI3K/Akt promote neurogenesis (3) Angiogenesis: G-CSF stimulates neutrophils or astrocytes to secrete VEGF, or directly mobilizes circulating endothelial progenitor cells (cEPCs) to promote angiogenesis within the CNS; and (4) The mobilization of autologous hemopoietic stem cells: G-CSF triggers the mobilization of autologous hemopoietic stem cells that migrate into ischemic brain, and thus significantly improve lesion repair.
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fig03: Possible mechanisms for neuroprotection of G-CSF in cerebral ischemia and neurodegeneration. G-CSF provokes multiple intracellular signal transductions including Jak/Stat, ERK and PI3K/Akt in neuroprotection. (1) Anti-apoptosis: G-CSF mediates antiapoptotic pathway through ERK or/and JAK/Stat signalling activation and subsequent upregulation of bcl-2 and inhibition of caspase- 3; (2) Neuronal differentiation: Stat regulates VEGF expression, or G-CSF activates endothelial cells to release BDNF.VEGF, BDNF and activated PI3K/Akt promote neurogenesis (3) Angiogenesis: G-CSF stimulates neutrophils or astrocytes to secrete VEGF, or directly mobilizes circulating endothelial progenitor cells (cEPCs) to promote angiogenesis within the CNS; and (4) The mobilization of autologous hemopoietic stem cells: G-CSF triggers the mobilization of autologous hemopoietic stem cells that migrate into ischemic brain, and thus significantly improve lesion repair.

Mentions: Administration of G-CSF is known to mobilize HSC from the bone marrow into the peripheral blood (Fig. 3). G-CSF application resulted in a significant decrease in infarct volume and enhanced survival rate, which may be mediated by the mobilization of autologous HSC in experimental cerebral ischemia [65, 66]. Our results demonstrated that subcutaneous injection of G-CSF increased the mobilization of circulating CD34+ cells which were seen around the perivascular in ischemic hemisphere, indicating that CD34+ cells mobilized with G-CSF can home from the circulating blood into the ischemic brain tissues [67]. Other studies have also showed that ischemic brain specifically attracted peripheral transplanted bone marrow stromal cells (BMSC) [68–70].


Cell biology and clinical promise of G-CSF: immunomodulation and neuroprotection.

Xiao BG, Lu CZ, Link H - J. Cell. Mol. Med. (2007 Nov-Dec)

Possible mechanisms for neuroprotection of G-CSF in cerebral ischemia and neurodegeneration. G-CSF provokes multiple intracellular signal transductions including Jak/Stat, ERK and PI3K/Akt in neuroprotection. (1) Anti-apoptosis: G-CSF mediates antiapoptotic pathway through ERK or/and JAK/Stat signalling activation and subsequent upregulation of bcl-2 and inhibition of caspase- 3; (2) Neuronal differentiation: Stat regulates VEGF expression, or G-CSF activates endothelial cells to release BDNF.VEGF, BDNF and activated PI3K/Akt promote neurogenesis (3) Angiogenesis: G-CSF stimulates neutrophils or astrocytes to secrete VEGF, or directly mobilizes circulating endothelial progenitor cells (cEPCs) to promote angiogenesis within the CNS; and (4) The mobilization of autologous hemopoietic stem cells: G-CSF triggers the mobilization of autologous hemopoietic stem cells that migrate into ischemic brain, and thus significantly improve lesion repair.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401293&req=5

fig03: Possible mechanisms for neuroprotection of G-CSF in cerebral ischemia and neurodegeneration. G-CSF provokes multiple intracellular signal transductions including Jak/Stat, ERK and PI3K/Akt in neuroprotection. (1) Anti-apoptosis: G-CSF mediates antiapoptotic pathway through ERK or/and JAK/Stat signalling activation and subsequent upregulation of bcl-2 and inhibition of caspase- 3; (2) Neuronal differentiation: Stat regulates VEGF expression, or G-CSF activates endothelial cells to release BDNF.VEGF, BDNF and activated PI3K/Akt promote neurogenesis (3) Angiogenesis: G-CSF stimulates neutrophils or astrocytes to secrete VEGF, or directly mobilizes circulating endothelial progenitor cells (cEPCs) to promote angiogenesis within the CNS; and (4) The mobilization of autologous hemopoietic stem cells: G-CSF triggers the mobilization of autologous hemopoietic stem cells that migrate into ischemic brain, and thus significantly improve lesion repair.
Mentions: Administration of G-CSF is known to mobilize HSC from the bone marrow into the peripheral blood (Fig. 3). G-CSF application resulted in a significant decrease in infarct volume and enhanced survival rate, which may be mediated by the mobilization of autologous HSC in experimental cerebral ischemia [65, 66]. Our results demonstrated that subcutaneous injection of G-CSF increased the mobilization of circulating CD34+ cells which were seen around the perivascular in ischemic hemisphere, indicating that CD34+ cells mobilized with G-CSF can home from the circulating blood into the ischemic brain tissues [67]. Other studies have also showed that ischemic brain specifically attracted peripheral transplanted bone marrow stromal cells (BMSC) [68–70].

Bottom Line: G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis.Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration.Our understanding of these novel sites of action of G-CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G-CSF from basic experiments to clinical patients.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. bgxiao@shmu.edu.cn

ABSTRACT
In the light of the enthusiasm to use of recombinant human granulocyte colony-stimulating factor (G-CSF) for immunomodulation and neuroprotection, it should be remembered that the current knowledge is based on a century of laborious research. G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis. Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration. Here, we describe the immunomodulation and the neuroprotection that can be achieved with G-CSF, and summarize possible mechanisms of G-CSF as a potential therapeutic agent in autoimmune diseases and neurological disorders. Our understanding of these novel sites of action of G-CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G-CSF from basic experiments to clinical patients.

Show MeSH
Related in: MedlinePlus