Lipopolysaccharide and hypoxia/ischemia induced IL-2 expression by microglia in neonatal brain.
Using a model of perinatal brain lesions induced by lipopolysaccharide and hypoxia/ischemia, we hypothesized that interleukin-2 (IL-2), a neurotoxic cytokine, was enhanced within injured brains. We showed that lipopolysaccharide and hypoxia/ischemia enhanced both intracerebral IL-2 mRNA and protein levels, with a maximum increase upon lipopolysaccharide and hypoxia/ischemia. The lack of detectable T lymphocytes suggested the synthesis of IL-2 by neural cells. Lipopolysaccharide and hypoxia triggered IL-2 synthesis by cultured microglia with a peak after exposure to lipopolysaccharide and hypoxia. Double-labeling showed, in vivo and in vitro, that IL-2 immunoreactivity was colocalized with a microglia/macrophage marker. These results disclosed the ability of microglia to produce IL-2 and also suggest the implication of IL-2 in neural cell death triggered by perinatal lipopolysaccharide and hypoxia/ischemia exposures.
Girard
Sylvie
S
Child Neurology Laboratory, Department of Pediatrics, Université de Sherbrooke, Quebec, Canada.
Larouche
Annie
A
Kadhim
Hazim
H
Rola-Pleszczynski
Marek
M
Gobeil
Fernand
F
Sébire
Guillaume
G
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D000860:Hypoxia / Q000473:pathology*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D007376:Interleukin-2; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2