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Publication : Potent pro-inflammatory actions of leukemia inhibitory factor in the spinal cord of the adult mouse.

First Author  Kerr BJ Year  2004
Journal  Exp Neurol Volume  188
Issue  2 Pages  391-407
PubMed ID  15246839 Mgi Jnum  J:94574
Mgi Id  MGI:3513504 Doi  10.1016/j.expneurol.2004.04.012
Citation  Kerr BJ, et al. (2004) Potent pro-inflammatory actions of leukemia inhibitory factor in the spinal cord of the adult mouse. Exp Neurol 188(2):391-407
abstractText  Injury in the peripheral or central nervous systems causes a significant rise in the levels of the pleiotropic cytokine leukemia inhibitory factor (LIF). This increase influences cell survival, reactive gliosis and inflammatory responses. Since prior work has focused primarily on peripheral nerve and brain, little is known about the role of LIF in the spinal cord injury response. We address this issue by examining the effects of injury in the LIF knockout (KO) mouse, as well as using an adenoviral vector to over-express LIF in the spinal cord of adult mice. We find that LIF over-expression results in a dramatic rise in cell proliferation, primarily in microglia/macrophages. Astrocytes are not stimulated to proliferate but are activated by the elevated LIF. LIF over-expression also causes the development of severe hindlimb motor dysfunction, an effect mediated by the enhanced activation of microglia/macrophages, as inhibiting microglial activation with minocycline attenuates these motor deficits. Conversely, proliferation is significantly diminished and the microglial/macrophage response to spinal cord injury is much less in the LIF KO compared to wild type (WT). Thus, LIF is a potent pro-inflammatory factor in the adult spinal cord and represents a potential target for the manipulation of inflammatory reactions after spinal cord injury.
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