Eicosanoid production by rat cerebral endothelial cells: Stimulation by lipopolysaccharide, interleukin-1 and interleukin-6

Vries, Helga E. de; Hoogendoorn, Karin H.; Dijk, J.J.M. van; Zijlstra, Freek J.; Dam, Anne‐Marie van; Breimer, D. D.; Berkel, Theo J.C. Van; Boer, Albertus G. de; Kuiper, Johan

doi:10.1016/0165-5728(95)00009-q

Cited by 60 publications

(26 citation statements)

References 28 publications

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“…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. 25,26 IL-1␤ dilates the canine basilar artery as a result of the COX-2 induction, but not via the formation of nitric oxide.…”

Section: Discussionsupporting

confidence: 80%

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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Section: Discussionsupporting

confidence: 80%

Inducible Cyclooxygenase Expression in Canine Basilar Artery After Experimental Subarachnoid Hemorrhage

Osuka

Suzuki

Watanabe

et al. 1998

Stroke

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“…The importance of the BBB for immune-to-brain signaling was acknowledged as the PGE2 synthesizing enzymes COX-2 and mPGES-1 were shown to be induced in the BBB by varying peripheral and central immune stimuli (Cao et al, 1995;Cao et al, 1996;Cao et al, 1998;Ek et al, 2001;Engblom et al, 2002), corroborating previous studies which suggested that BBB was a source of PGE2 (Bishai et al, 1987;Devries et al, 1995;Van Dam et al, 1993). Subsequently it was also demonstrated that the BBB is a cytokine target, presenting receptors for IL-1β (Ek et al, 2001;Ericsson et al, 1995;Konsman et al, 2004), IL-6 (Vallieres and Rivest, 1997) and TNFα (Nadeau and Rivest, 1999a) as well as intracellular cytokine activation markers like IkBα (Laflamme and Rivest, 1999;Quan et al, 1997) and SOCS3 (Lebel et al, 2000).…”

Section: The Bbb As An Interface For Immune Signal-transductionsupporting

confidence: 75%

Talking to the Brain at the Blood-Brain Barrier through Inflammation-Induced Prostaglandin E2

Vasilache¹

2015

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The immune-to-brain signaling is a critical survival factor when the body is confronted by pathogens, and in particular by microorganisms. During infections, the ability of the immune system to engage the central nervous system (CNS) in the management of the inflammatory response is just as important as its ability to mount a specific immune response against the pathogen, since the CNS can provide a systemic negative feed-back to the immune activation by release of stress hormones and also can prioritize the usage of the energy resources by the vital organs. Prostaglandin E2 (PGE2) and pro-inflammatory cytokines were among the first mediators to be identified to participate in the immune-to-brain signaling, a process that is clinically recognized by the development of manifestations of common illness such as fever, anorexia, decreased social interactions, lethargy, sleepiness, and hyperalgesia.In this thesis the contribution of PGE2 to the immune-to-brain signaling was further characterized at the blood-brain-barrier (BBB) and in the anterior preoptic area (POA) of the hypothalamus (i.e. the thermoregulatory region or, in sickness, the fever generating region).BBB is the major interface region between peripheral circulating cytokines and the neuronal parenchyma and a critical source of PGE2. Using chimeric mice lacking the inducible enzyme for PGE2 synthesis, microsomal PGE synthase-1 (mPGES-1), in either hematopoietic or nonhematopoietic cells, we demonstrate in paper I that brain endothelial cells are the critical source of PGE2 in BBB during peripheral inflammation. For the demonstration of the mPGES-1 expression in the BBB cells we developed in paper I a method for enzymatic dissociation of these cells, followed by fluorescence activated cell sorting (FACS). Using the same method, we show in paper II that the BBB response to immune stimuli is towards an increased production of PGE2 in endothelial cells and an increased sensitivity of these cells for proinflammatory cytokines. These changes are supported by decreased PGE2 degradation and decreased synthesis of other prostanoids in perivascular macrophages, which hence respond in concordance with the endothelial cells in enhancing PGE2 signaling.Once released in the neuronal tissue, PGE2 has been shown to be critical for the fever response by acting on the type 3 PGE2 receptors (EP3) within POA. By laser capture microdissection (LCM) we extracted the EP3 receptor expressing region in POA, defined by in situ hybridization histochemistry, from mouse brain sections. We demonstrate in paper III that the predominant subtypes of the EP3 receptor in POA are EP3α and EP3γ. In paper IV we further analyze the effect of PGE2 on the LCM dissected EP-rich POA using gene expression microarrays. We demonstrate that PGE2 has a limited effect on the gene expression changes within POA, suggesting that the neuronal activity is modulated by PGE2 in a transcriptionindependent manner and that the profound gene expression changes that are seen in the CNS during inflammation ...

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“…LPS and cytokines synergistically increase cyclooxygenase 2 mRNA expression in BBB EC and potently stimulate prostanoid, in particular PGE 2 , production (DeVries et al 1995;Cao et al 1996;Rivest, 1999). Non-specific cyclooxygenase inhibitors attenuate the anorectic effects of LPS and IL-1b (Langhans et al 1989.…”

Section: Mediators Downstream Of Cytokinesmentioning

confidence: 99%

Signals generating anorexia during acute illness

Langhans

2007

Proc. Nutr. Soc.

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Anorexia is part of the body's acute-phase response to illness. Microbial products such as lipopolysaccharides (LPS), which are also commonly used to model acute illness, trigger the acute-phase response and cause anorexia mainly through pro-inflammatory cytokines. LPS stimulate cytokine production through the cell-surface structural molecule CD14 and toll-like receptor-4. Cytokines ultimately change neural activity in brain areas controlling food intake and energy balance. The blood-brain barrier endothelial cells (BBB EC) are an important site of cytokine action in this context. BBB EC and perivascular cells (microglia and macrophages) form a complex regulatory interface that modulates neuronal activity by the release of messengers (e.g. PG, NO) in response to peripheral challenges. Serotonergic neurons originating in the raphe nuclei and glucagon-like peptide-1-expressing neurons in the hindbrain may be among the targets of these messengers, because serotonin (5-HT), acting through the 5-HT 2C receptor, and glucagon-like peptide-1 have recently emerged as neurochemical mediators of LPS anorexia. The central melanocortin system, which is a downstream target of serotonergic neurons, also appears to be involved in mediation of LPS anorexia. Interestingly, LPS also reduce orexin expression and the activity of orexin neurons in the lateral hypothalamic area of fasted mice. As the eating-stimulatory properties of orexin are apparently related to arousal, the inhibitory effect of LPS on orexin neurons might be involved in LPS-induced inactivity and anorexia. In summary, the immune signalling pathways of LPS-induced, and presumably acute illness-induced, anorexia converge on central neural signalling systems that control food intake and energy balance in healthy individuals.

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Eicosanoid production by rat cerebral endothelial cells: Stimulation by lipopolysaccharide, interleukin-1 and interleukin-6

Cited by 60 publications

References 28 publications

Inducible Cyclooxygenase Expression in Canine Basilar Artery After Experimental Subarachnoid Hemorrhage

Inducible Cyclooxygenase Expression in Canine Basilar Artery After Experimental Subarachnoid Hemorrhage

Talking to the Brain at the Blood-Brain Barrier through Inflammation-Induced Prostaglandin E2

Signals generating anorexia during acute illness

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