Leukemia inhibitory factor is an autocrine survival factor for Schwann cells.
Schwann cells play a major role in promoting nerve survival and regeneration after injury. Their activities include providing neurotrophic factors and increasing the production of extracellular matrix components and cell surface adhesion molecules to promote axon regeneration. Following nerve transection, leukemia inhibitory factor (LIF) is up-regulated by Schwann cells at the injury site. LIF receptors are also up-regulated at the nerve injury site, but their cellular localization and function have not been fully characterized. We demonstrate that Schwann cells express mRNAs for LIF and the LIF receptor components LIF receptor subunit beta and glycoprotein 130 in vitro. We also show that although LIF is not required for the genesis of Schwann cells, it can potentiate the survival of differentiated Schwann cells in the context of neuregulin support. Not only does exogenous LIF promote survival under these conditions, but addition of the soluble LIF receptor (LIF binding protein) and anti-LIF antibodies significantly reduced cell survival, suggesting that LIF exerts autocrine effects. These results suggest that Schwann cell survival following nerve injury is potentially modulated by LIF.
Dowsing
B J
BJ
Bernard O'Brien Institute of Microsurgery, St. Vincent's Hospital, Melbourne, Victoria, Australia.
Morrison
W A
WA
Nicola
N A
NA
Starkey
G P
GP
Bucci
T
T
Kilpatrick
T J
TJ
D000818:Animals; D002455:Cell Division; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004622:Embryo, Mammalian; D017353:Gene Deletion; D015870:Gene Expression; D006131:Growth Inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology; D053606:Receptors, OSM-LIF; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000502:physiology*; D012584:Sciatic Nerve / Q000166:cytology
D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D004247:DNA