Interleukin-1β and Interleukin-6 Specifically Increase the Release of Prostaglandin E&lt;sub&gt;2&lt;/sub&gt; from Rat Hypothalamic Explants in vitro

Navarra, Pierluigi; Pozzoli, Giacomo; Brunetti, Luigi; Ragazzoni, Enzo; Besser, Michael; Grossman, Ashley

doi:10.1159/000126209

Cited by 88 publications

(27 citation statements)

References 9 publications

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“…These results are in accordance with our previous work showing that LPS induces PGE2 synthesis in rat cortical slices [7], Further more. previous findings showing that IL-1 can increase PGE2 production in hypothalamic explants [14] and with other experiments have shown that intravenous injection of IL-1 in conscious rats caused a pronounced increase in brain PGE2 in the organum vasculosum of the lamina terminalis, dorsal hippocampus and hypotha lamic paraventricular nucleus, as measured by microdia lysis [13,33].…”

Section: Discussionsupporting

confidence: 52%

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Effect of Bacterial Endotoxin and Interleukin-1 on Prostaglandin Biosynthesis by the Hippocampus of Mouse Brain: Role of Interleukin-1 Receptors and Glucocorticoids

1995

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There is increasing evidence indicating that the production of cytokines and prostaglandins (PG) may be interrelated and is regulated by glucocorticoids (GC). In the present study we examined the effect of the bacterial endotoxin lipopolysaccharide (LPS) and interleukin-1 (IL-1) on the ex vivo production of PGE₂ by the dorsal hippocampus of the mouse which contains high levels of receptors to IL-1. The roles of IL-1 receptors and GC in the regulation of LPS- or IL-1-induced PGE₂ production were also studied. In control mice the basal rate of PGE₂ ex vivo synthesis by slices of dorsal hippocampus was about 250 pg/mg protein/60 min. Intraperitoneal injection of either LPS (1-50 µg/mouse) or IL-1α (50-200 ng/mouse) increased the production of PGE₂ in a dose- and time-dependent manner. Both LPS and IL-lα induced a maximal 2.5-fold increase in PGE₂ production at 6 h after the injections. IL-1β was less effective by approximately 30% as compared to IL-1α. In mice treated with the IL-1 receptor antagonist or with the IL-1 antagonist α-melanocyte-stimulating hormone (α-MSH), the effects of LPS and IL-1 on PGE₂ production were completely abolished. Intraperitoneal injections of dexamethasone (DEX) 5 or 30 µg/mouse 2 h prior to the administration of IL-1α significantly enhanced the effect of the cytokine on PGE₂ production. In mice treated with 100 µg DEX/mouse, the facilitatory effect of the lower DEX doses in IL-1-induced PGE₂ production was abolished. In adrenalectomized mice (6 days), the administration of IL-1 failed to affect hippocampal PGE₂ production. Injection of DEX (30 µg/mouse) 18 and 2 h prior to IL-1α restored the effect of IL-lα on the production of PGE₂. These results suggest: LPS and IL-1α or β can stimulate PGE₂ biosynthesis by the mouse dorsal hippocampus; this effect is mediated by the specific IL-1 receptors and can be antagonized by α-MSH; in the mouse, GC may exert a permissive, a stimulatory or an inhibitory effect on IL-1-induced PGE₂ hippocampal production. The relative intensity of each of these effects depend on the level of circulating GC.

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Section: Discussionsupporting

confidence: 52%

“…The functional impor tance of PG production in the brain has not been fully such as bacterial endotoxin (lipopolysaccharide, LPS) and cvtokines can activate the synthesis of PG in brain tissue [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Effect of Bacterial Endotoxin and Interleukin-1 on Prostaglandin Biosynthesis by the Hippocampus of Mouse Brain: Role of Interleukin-1 Receptors and Glucocorticoids

1995

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“…6 -8 Many lines of evidence have confirmed that these cytokines have effects mediated via stimulation of the prostanoid cascade within the CNS. IL-6 induces fever through formation of prostanoids in rats 23 and stimulates production of PGE 2 in the rat hypothalamus 24 and cerebral arteries. 25 We also demonstrated that the concentration of PGE 2 in CSF becomes elevated over preinjection concentrations by 4.5 hours after intracisternal injection of IL-6 (data not shown), in accordance with the findings of Dinarello et al 26 The effect of IL-1␤ on the production of eicosanoids by endothelial cells is more potent than that of IL-6.…”

Section: Discussionmentioning

confidence: 99%

Inducible Cyclooxygenase Expression in Canine Basilar Artery After Experimental Subarachnoid Hemorrhage

Osuka

Suzuki

Watanabe

et al. 1998

Stroke

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Background and Purpose —Inducible cyclooxygenase (COX-2) has been found to play a pathological role in cerebral insult . We investigated the expression of COX-2 in the basilar artery after experimental subarachnoid hemorrhage (SAH). Methods —In a canine “two-hemorrhage” model of SAH, the basilar arteries were obtained on day 2 after a cisternal injection of autologous blood or on days 4, 6, 7, or 9 after the second injection. Basilar arteries also were obtained 12 hours after intracisternal injection a cytokine: interleukin (IL)-1β (0.03 μg), IL-6 (3 μg), or IL-8 (10 μg). Western blotting with a polyclonal anti–COX-2 antibody was performed in these arteries. Results —COX-2 protein was not demonstrated in the basilar artery in control animals without SAH. However, it was expressed in the basilar artery on days 2, 4, 6, and 7 after blood injection but not on day 9 . Intracisternal injection of IL-1β, IL-6, or IL-8 also induced COX-2 in the basilar artery. Conclusions —COX-2 expression was detected in basilar arterial tissue in both acute and chronic stages after SAH. Elevation of inflammatory cytokines after SAH may be involved in the induction of COX-2, which may produce sufficient quantities of eicosanoids to affect hemodynamics after SAH.

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“…The exact PG subtype(s) and the site(s) of action involved in these effects still remain unclear, but a large body of evidence indicates that PG of E 2 type is a key molecule in the transfer of information received from circulating cytokines and foreign materials to parenchymal cells of the brain. IL-1 increases the release of PGE 2 from rat hypothalamic explants in vitro 33 and numerous regions of the brain in vivo, including the paraventricular nucleus of the hypothalamus (PVN). 34 Intracerebral administration of PGE 2 elevates plasma ACTH and corticosterone 35,36 and causes a selective cellular activation as indicated by the rapid and transient expression of the immediateearly gene (IEG) c-fos mRNA and its protein product within multiple regions of the brain recognized to be activated during the acute-phase response.…”

Section: What Are the Functional Consequences Of Pg Production By Celmentioning

confidence: 99%

What is the cellular source of prostaglandins in the brain in response to systemic inflammation? Facts and controversies

Rivest

1999

Mol Psychiatry

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Circulating inflammatory mediators can signal neurons through a pathway in which cytokine activation of the cells of the blood-brain barrier causes the induction of the nuclear factor kappa B (NF-B), leading to the transcription of target genes, such as the one encoding cyclooxygenase 2 (COX-2), the enzyme that initiates prostaglandin formation. These active products of the arachidonate metabolism produced by the cerebral microvasculature have critical roles in initiating the neuronal responses and the neurophysiological outcomes that take place during immunogenic stimuli, including sickness behaviors, fever and increase in the hypothalamic-pituitary adrenal axis. Whether there is more than a single cell type in the blood-brain barrier responsible for the synthesis of prostanoids in the presence of circulating proinflammatory cytokines is an interesting debate that will be summarized here.

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Interleukin-1β and Interleukin-6 Specifically Increase the Release of Prostaglandin E<sub>2</sub> from Rat Hypothalamic Explants in vitro

Cited by 88 publications

References 9 publications

Effect of Bacterial Endotoxin and Interleukin-1 on Prostaglandin Biosynthesis by the Hippocampus of Mouse Brain: Role of Interleukin-1 Receptors and Glucocorticoids

Effect of Bacterial Endotoxin and Interleukin-1 on Prostaglandin Biosynthesis by the Hippocampus of Mouse Brain: Role of Interleukin-1 Receptors and Glucocorticoids

Inducible Cyclooxygenase Expression in Canine Basilar Artery After Experimental Subarachnoid Hemorrhage

What is the cellular source of prostaglandins in the brain in response to systemic inflammation? Facts and controversies

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