title: Chemokines and inflammatory mediators interact to regulate adult murine neural precursor cell proliferation, survival and differentiation.
abstract: Adult neural precursor cells (NPCs) respond to injury or disease of the CNS by migrating to the site of damage or differentiating locally to replace lost cells. Factors that mediate this injury induced NPC response include chemokines and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ), which we have shown previously promotes neuronal differentiation. RT-PCR was used to compare expression of chemokines and their receptors in normal adult mouse brain and in cultured NPCs in response to IFNγ and TNFα. Basal expression of many chemokines and their receptors was found in adult brain, predominantly in neurogenic regions, with OB≫SVZ>hippocampus and little or no expression in non-neurogenic regions, such as cortex. Treatment of SVZ-derived NPCs with IFNγ and TNFα (alone and in combination) resulted in significant upregulation of expression of specific chemokines, with CXCL1, CXCL9 and CCL2 most highly upregulated and CCL19 downregulated. Unlike IFNγ, chemokine treatment of NPCs in vitro had little or no effect on survival, proliferation or migration. Neuronal differentiation was promoted by CXCL9, CCL2 and CCL21, while astrocyte and total oligodendrocyte differentiation was not affected. However, IFNγ, CXCL1, CXCL9 and CCL2 promoted oligodendrocyte maturation. Therefore, not only do NPCs express chemokine receptors, they also produce several chemokines, particularly in response to inflammatory mediators. This suggests that autocrine or paracrine production of specific chemokines by NPCs in response to inflammatory mediators may regulate differentiation into mature neural cell types and may alter NPC responsiveness to CNS injury or disease.
authors.affiliation: Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Alisa
authors.initials: A
authors.lastname: Turbic
authors.forename: Soo Yuen
authors.initials: SY
authors.lastname: Leong
authors.forename: Ann M
authors.initials: AM
authors.lastname: Turnley
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000378:metabolism / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology; D054360:Chemokine CXCL1 / Q000378:metabolism / Q000494:pharmacology; D054370:Chemokine CXCL9 / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D054415:Chemokine CCL19; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D054370:Chemokine CXCL9; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma