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Review
. 2007 Nov-Dec;11(6):1272-90.
doi: 10.1111/j.1582-4934.2007.00101.x.

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

Bao-Guo Xiao  1 , Chuan-Zhen Lu, Hans Link
Affiliations
Review

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

Bao-Guo Xiao et al. J Cell Mol Med. 2007 Nov-Dec.

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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Figures

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Possible mechanisms of immunomodulation of G-CSF in adaptive immunity.G-CSF induces the expression of both GATA-3 and SOCS3, which control T helper cell differentiation, and directs to Th2 response. G-CSF directly induces the generation of tolerogenic DC, or indirectly drives the production of tolerogenic DC through inducing SOCS3 expression.Tolerogenic DC have the capacity to induce a regulatory T cells or/and Th2 immune responses. Despite our limited knowledge about the molecular mechanisms involved, it is clear that G-CSF treatment results in increase in the number of regulatory T cells and the differentiation of Th2 cells. G-CSF-induced SOCS3 in turn limits G-CSF receptor signalling.
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G-CSF-mediated neuroprotection in cerebral ischemia. (a-A) Survival rate of rats with cerebral ischemia treated with G-CSF and with saline as control, (a-B) Infarction volume and (a-C) Neurological Severity Score. (b) Double-labelled immunofluorescent staining of brain slices obtained from G-CSF-treated rats at day 7 after MCAO. Red images correspond to Brdu, GFAP or nestin and green images to fibronectin or BDNF.Yellow images reveal double-labelled positive cells. (c) G-CSF receptor expression in GFAP+ astrocytes in ischemic region (B), but not in non-ischemic region (A). Red images correspond to GFAP and green images to G-CSF receptor.Yellow images show double-labelled positive cells. (d) Area of cell death stained with PI (up) and number of bcl-2+ cells (down) at 7 days after hippocampal slice cultures in the absence (A) or presence (B) of G-CSF. (e) Expression of nestin, vWF and MAP-2 expression brain sections.The immunohistochemistry of nestin (A and B), vWF (C and D) and MAP-2 (E and F) are performed on brain slices obtained from G-CSF-treated rats and control rats at day 7 after MCAO.
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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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Possible mechanisms for G-CSF-mediated neuroprotection via immunomodulation. G-CSF polarizes T cell differentiation from Th1 to Th2 cells and induces Th2 responses, or relies on tolerogenic DC to generate regulatory T cells, which can enter into the CNS to contribute to the neuroprotective microenvironment through producing BDNF, IL-4, IL-10 and TGF-b. In addition, G-CSF, as an anti-inflammatory agent, can reduce levels of IFN-γ, IL-1β, IL-6, TNF-α and iNOS production in order to co-construct the neuroprotective microenvironment.
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References

    1. Welte K, Gabrilove J, Bronchud MH, Platzer E, Morstyn G. Filgrastim (r-metHuG-CSF): the first 10 years. Blood. 1996;88:1907–29. - PubMed
    1. Aladdin H, Ullum H, Dam Nielsen S, Espersen C, Mathiesen L, Katzenstein TL, Gerstoft J, Skinhoj P, Pedersen BK. Granulocyte colony-stimulating factor increases CD4+ T cell counts of human immunodeficiency virus-infected patients receiving stable, highly active antiretroviral therapy: results from a randomized, placebo-controlled trial. J Infect Dis. 2000;181:1148–52. - PubMed
    1. Klangsinsirikul P, Russell NH. Peripheral blood stem cell harvests from G-CSF-stimulated donors contain a skewed Th2 CD4 phenotype and a predominance of type 2 dendritic cells. Exp Hematol. 2002;30:495–501. - PubMed
    1. Agnello D, Mascagni P, Bertini R, Villa P, Senaldi G, Ghezzi P. Granulocyte colony-stimulating factor decreases tumor necrosis factor production in whole blood: role of interleukin-10 and prostaglandin E(2) Eur Cytokine Netw. 2004;15:323–6. - PubMed
    1. Rutella S, Pierelli L, Bonanno G, Sica S, Ameglio F, Capoluongo E, Mariotti A, Scambia G, D'Onofrio G, Leone G. Role for granulocyte colonystimulating factor in the generation of human T regulatory type 1 cells. Blood. 2002;100:2562–71. - PubMed

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