Leukemia inhibitory factor promotes oligodendrocyte survival after spinal cord injury.
Injury to the mammalian spinal cord is accompanied by a delayed, secondary wave of oligodendrocyte apoptosis that arises several days after the initial injury. A strong candidate to support oligodendrocyte survival after spinal cord injury is the pleiotropic cytokine, leukemia inhibitory factor (LIF). In vitro, LIF potentiates the differentiation and survival of oligodendrocyte precursors. LIF can also prevent oligodendrocyte apoptosis in response to either growth factor removal or cytotoxic challenge. More recently, in vivo studies have demonstrated that LIF is effective in preventing oligodendrocyte death in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). We therefore asked whether systemic delivery of LIF could ameliorate oligodendrocyte death in a mouse model of spinal cord injury. We have found that daily administration of LIF (25 microg/kg/day) promotes oligodendrocyte survival after spinal cord injury. Interestingly however, this effect does not appear to be mediated by a direct action of LIF on the oligodendrocyte but rather via an ancillary cell type, which results in augmented expression of another trophic factor capable of supporting oligodendrocyte survival, insulin-like growth factor 1 (IGF-1).
Kerr
Bradley J
BJ
Biology Division, California Institute of Technology, Pasadena, California, USA. bradley.kerr@mail.mcgill.ca
Patterson
Paul H
PH
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D018121:Receptors, Cytokine / Q000187:drug effects / Q000378:metabolism; D053606:Receptors, OSM-LIF; D013119:Spinal Cord Injuries / Q000473:pathology*
D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D016177:Macrophage-1 Antigen; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D007334:Insulin-Like Growth Factor I; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases