Evidence that the interleukin-1 beta-induced prostaglandin E2 release from rat hypothalamus is mediated by type I and type II interleukin-1 receptors.
Interleukin-1 beta (IL-1 beta) has been shown to specifically increase the release of prostaglandin (PG) E2 from rat hypothalamic explants in short-term experiments. In this study we attempted to characterize the receptor subtype(s) involved in this response. Rat hypothalamic explants were incubated with mouse monoclonal antibodies (mAbs) raised against human IL-1 type I or type II receptors, IL-1 receptor antagonist (IL-1ra) and alpha-melanocyte-stimulating hormone (alpha-MSH) (which appears to antagonize certain IL-1 induced inflammatory effects in vivo), alone and in the presence of IL-1 beta. PGE2 released into the incubation medium was measured by radioimmunoassay. The anti-type I mAb reduced both basal and IL-1 beta-stimulated PGE2 release at 10 micrograms/ml, but not at lower concentrations. The anti-type II mAb also produced a significant decrease in stimulated release but had no effect on basal release. IL-1ra mimicked the effects of the anti-type I mAb, while alpha-MSH failed to alter either basal or stimulated PGE2 release. These findings suggest that IL-1 beta controls production and release of PGE2 by the rat hypothalamus via both type I and type II receptors, although the latter appear to be involved only in the response to high levels of IL-1.
Mirtella
A
A
Department of Pharmacology, Catholic University School of Medicine, Rome, Italy.
Tringali
G
G
Guerriero
G
G
Ghiara
P
P
Parente
L
L
Preziosi
P
P
Navarra
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015232:Dinoprostone / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D007158:Immunologic Techniques; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000502:physiology*; D012795:Sialoglycoproteins / Q000494:pharmacology; D000521:alpha-MSH / Q000494:pharmacology
D000911:Antibodies, Monoclonal; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D000521:alpha-MSH; D015232:Dinoprostone