Leukemia inhibitory factor modulates production of inflammatory mediators and myelin phagocytosis by macrophages.
Leukemia inhibitory factor (LIF) promotes survival of glial cells and neurons during autoimmune and injury responses in the central nervous system (CNS). While various studies indicate that LIF also modulates ongoing inflammatory responses, data on underlying events are lacking. In this study we demonstrate that LIF modulates macrophage function. LIF inhibits the production of oxygen radicals and TNFalpha and stimulates myelin uptake by macrophages. These effects of LIF are accompanied by activation of the JAK/STAT3 signalling pathway. Our findings demonstrate that LIF has anti-inflammatory properties and enhances myelin clearance, implicating that LIF may be an important factor in CNS inflammatory disease.
Hendriks
Jerome J A
JJ
Hasselt University, Biomedical Research Institute (BIOMED), Diepenbeek, Belgium.
Slaets
Helena
H
Carmans
Sofie
S
de Vries
Helga E
HE
Dijkstra
Christine D
CD
Stinissen
Piet
P
Hellings
Niels
N
D000818:Animals; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology*; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D050822:Cytokine Receptor gp130; D051058:Oncogene Protein v-akt; D048052:Mitogen-Activated Protein Kinase 3