Characterization of interleukin-1 receptor antagonist isoform expression in the brain of lipopolysaccharide-treated rats.
The endogenous interleukin-1 receptor antagonist is the natural inhibitor of the biological effects of interleukin-1 during inflammation. Interleukin-1 receptor antagonist refers to three isoforms: one secreted and two intracellular forms (types I and II). The objective of the present study was to investigate the expression of interleukin-1 receptor antagonist isoforms in the rat brain in vivo in response to an i.p. injection of lipopolysaccharide. The interleukin-1 receptor antagonist was studied at the messenger and protein levels by reverse transcription-polymerase chain reaction and western blot analysis, respectively. Interleukin-1 receptor antagonist messenger RNA was constitutively expressed in the brain and its expression increased in response to lipopolysaccharide. The three interleukin-1 receptor antagonist protein isoforms were up-regulated after lipopolysaccharide treatment in a time-dependent manner. Their relative expression differed according to the isoform and brain region studied. Double immunofluorescence staining revealed interleukin-1 receptor antagonist positive neurons and microglia in hippocampus 24h after lipopolysaccharide stimulation. These results demonstrate for the first time that brain cells are able to produce interleukin-1 receptor antagonist isoforms in response to a peripheral immune challenge with a predominance of the secreted over intracellular forms.
Palin
K
K
INSERM U.394, Rue C. Saint-Saëns, 33077 Bordeaux Cedex, France. Karine.Palin@bordeaux.inserm.fr
Pousset
F
F
Verrier
D
D
Dantzer
R
R
Kelley
K
K
Parnet
P
P
Lestage
J
J
D015153:Blotting, Western; D001921:Brain / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D010902:Pituitary Gland / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D020033:Protein Isoforms; D012333:RNA, Messenger; D012795:Sialoglycoproteins