title: The dual role of CXCL8 in human CNS stem cell function: multipotent neural stem cell death and oligodendrocyte progenitor cell chemotaxis.
abstract: Research into multiple sclerosis (MS) has shown that cells purportedly important to myelin repair within the CNS, namely neural stem cells (NSC) and oligodendrocyte progenitor cells (OPC), are recruited to active lesion sites during the course of the disease. However, over time these cells appear to become depleted or functionally blocked in and around lesions, accompanied by a failure of repair mechanisms. We have previously demonstrated elevated CXCL8 in patients with MS, and hypothesized that this chemokine may play a role in the pathology of this disease. Using NSC and OPC derived in vitro from human embryonic stem cells (hESC) we demonstrate here that CXCL8 has a dual role on stem cell biology in vitro. CXCL8 caused CXCR1-mediated death of NSC, but not OPC, whilst also acting as a potent chemoattractant for both cell types. These data support a context-dependent role for CXCL8 expression in the CNS in which it may drive recruitment of NSC and OPC to sites of inflammation, but as a side-effect could also contribute to the failure of myelin repair in MS.
authors.affiliation: Department of Neurology, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA.
authors.forename: Eve E
authors.initials: EE
authors.lastname: Kelland
authors.forename: Wendy
authors.initials: W
authors.lastname: Gilmore
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Weiner
authors.forename: Brett T
authors.initials: BT
authors.lastname: Lund
mesh_terms: D016923:Cell Death / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000473:pathology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*; D039902:Multipotent Stem Cells / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D061251:Primary Cell Culture
chemical_list: D016209:Interleukin-8