Dexamethasone up-regulates type II IL-1 receptor in mouse primary activated astrocytes.
Brain astrocytes play a pivotal role in the brain response to inflammation. They express IL-1 receptors including the type I IL-1 receptor (IL-1RI) that transduces IL-1 signals in cooperation with the IL-1 receptor accessory protein (IL-1RAcP) and the type II IL-1 receptor (IL-1RII) that functions as a decoy receptor. As glucocorticoid receptors are expressed on astrocytes, we hypothesized that glucocorticoids regulate IL-1 receptors expression. IL-1beta-activated mouse primary astrocytes were treated with 10(-6) M dexamethasone, and IL-1 receptors were studied at the mRNA and protein levels. Using RT-PCR, IL-1RI and IL-1RII but not IL-1RAcP mRNAs were found to be up-regulated by dexamethasone in a time-dependent manner. Dexamethasone (Dex), but not progesterone, had no effect on IL-1RI but strongly increased IL-1RII mRNA expression. Binding studies revealed an increase in the number of IL-1RII binding sites under the effect of Dex, but no change in affinity. These findings support the concept that glucocorticoids have important regulatory effect on the response of astrocytes to IL-1.
Pousset
F
F
INSERM U.394, Institut F. Magendie, Bordeaux, France.
Cremona
S
S
Dantzer
R
R
Kelley
K W
KW
Parnet
P
P
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D053577:Interleukin-1 Receptor Accessory Protein; D051379:Mice; D008815:Mice, Inbred Strains; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*
D005938:Glucocorticoids; C507767:Il1rap protein, mouse; D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D003907:Dexamethasone