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Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro

Sugiura, Shigeki and Lahav, Ronit and Han, Jing and Kou, Shi-Ying and Banner, Lisa R. and de Pablo, Flora and Patterson, Paul H. (2000) Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro. European Journal of Neuroscience, 12 (2). pp. 457-466. ISSN 0953-816X. https://resolver.caltech.edu/CaltechAUTHORS:20160411-104137831

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Abstract

The cytokine leukaemia inhibitory factor (LIF) is up-regulated in glial cells after injury to the peripheral and central nervous systems. In addition, LIF is required for the changes in neuropeptide expression that normally occur when the axons of sympathetic and sensory neurons are transected. We investigated whether LIF is also necessary for the initial inflammatory response that follows mechanical injury to the sciatic nerve and cerebral cortex of adult mice. We find that inflammatory cell infiltration into crushed sciatic nerve is significantly slower in LIF knock-out (KO) mice compared with wild-type (WT) mice. Similarly, the microglial and astroglial responses to surgical injury of the cortex are significantly slower in LIF KO mice compared with WT mice. Consistent with these in vivo results, LIF is chemotactic for peritoneal macrophages in a microchamber culture assay. Thus, LIF is a key regulator of neural injury in vivo, where it is produced by glia and can act directly on neurons, glia and inflammatory cells. We also find that the initial inflammatory response to cortical injury is diminished in interleukin (IL)-6 KO mice. Surprisingly, however, the inflammatory response in LIF-IL-6 double KO mice is very similar to that of the single KO mice, suggesting that these cytokines may act in series rather than in parallel in this response.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1046/j.1460-9568.2000.00922.xDOIArticle
http://onlinelibrary.wiley.com/doi/10.1046/j.1460-9568.2000.00922.x/abstractPublisherArticle
Additional Information:© 2000 European Neuroscience Association. Received 15 June 1999, revised 12 October 1999, accepted 14 October 1999. First published: February 2000. We thank Doreen McDowell for administrative help, and Joanna Jankowsky and Sigrid Schwarz for providing comments on the manuscript, and K. Matsushima and M. Akiyama for technical advice on the chemotaxis assays. This work was supported by a grant to P.H.P. from the NINDS, and fellowships from the Japanese Research Foundation for Clinical Pharmacology (S.S.) and the Della Martin Foundation (R.L. and L.R.B.).
Funders:
Funding AgencyGrant Number
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
Japanese Research Foundation for Clinical PharmacologyUNSPECIFIED
Della Martin FoundationUNSPECIFIED
Subject Keywords:chemotaxis; cytokine; inflammatory response; leukemia inhibitory factor; interleukin-6
Issue or Number:2
Record Number:CaltechAUTHORS:20160411-104137831
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160411-104137831
Official Citation:Sugiura, S., Lahav, R., Han, J., Kou, S.-Y., Banner, L. R., De Pablo, F. and Patterson, P. H. (2000), Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro. European Journal of Neuroscience, 12: 457–466. doi:10.1046/j.1460-9568.2000.00922.x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66047
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:12 Apr 2016 21:09
Last Modified:03 Oct 2019 09:53

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