scholarly journals The Role of Interleukin-6 in Lipopolysaccharide-Induced Fever by Mechanisms Independent of Prostaglandin E2

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1850-1860 ◽  
Author(s):  
Camilla Nilsberth ◽  
Louise Elander ◽  
Namik Hamzic ◽  
Maria Norell ◽  
Johanna Lönn ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Knockout Mice ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Wild Type ◽  
Febrile Response ◽  
Prostaglandin E Synthase ◽  
Genotype Difference ◽  
The Relationship

Fever has been shown to be elicited by prostaglandin E2 (PGE2) binding to its receptors on thermoregulatory neurons in the anterior hypothalamus. The signals that trigger PGE2 production are thought to include proinflammatory cytokines, such as IL-6. However, although the presence of IL-6 is critical for fever, IL-6 by itself is not or only weakly pyrogenic. Here we examined the relationship between IL-6 and PGE2 in lipopolysaccharide (LPS)-induced fever. Immune-challenged IL-6 knockout mice did not produce fever, in contrast to wild-type mice, but the expression of the inducible PGE2-synthesizing enzymes, cyclooxygenase-2 and microsomal prostaglandin E synthase-1, was similarly up-regulated in the hypothalamus of both genotypes, which also displayed similarly elevated PGE2 levels in the cerebrospinal fluid. Nevertheless, both wild-type and knockout mice displayed a febrile response to graded concentrations of PGE2 injected into the lateral ventricle. There was no major genotype difference in the expression of IL-1β and TNFα or their receptors, and pretreatment of IL-6 knockout mice with soluble TNFα receptor ip or intracerebroventricularly or a cyclooxygenase-2 inhibitor ip did not abolish the LPS unresponsiveness. Hence, although IL-6 knockout mice have both an intact PGE2 synthesis and an intact fever-generating pathway downstream of PGE2, endogenously produced PGE2 is not sufficient to produce fever in the absence of IL-6. The findings suggest that IL-6 controls some factor(s) in the inflammatory cascade, which render(s) IL-6 knockout mice refractory to the pyrogenic action of PGE2, or that it is involved in the mechanisms that govern release of synthesized PGE2 onto its target neurons.

scholarly journals Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Naoto Muraoka ◽  
Kaori Nara ◽  
Fumiya Tamura ◽  
Hidenori Kojima ◽  
Hiroyuki Yamakawa ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E

scholarly journals Microparticles stimulate the synthesis of prostaglandin E2 via induction of cyclooxygenase 2 and microsomal prostaglandin E synthase 1

2007 ◽  
Vol 56 (11) ◽  
pp. 3564-3574 ◽  
Author(s):  
Astrid Jüngel ◽  
Oliver Distler ◽  
Ursula Schulze-Horsel ◽  
Lars C. Huber ◽  
Huy Riem Ha ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Prostaglandin E Synthase ◽  
Microsomal Prostaglandin E Synthase

scholarly journals Interleukin (IL)-6, But Not IL-1, Induction in the Brain Downstream of Cyclooxygenase-2 Is Essential for the Induction of Febrile Response against Peripheral IL-1α

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5044-5048 ◽  
Author(s):  
Kyoko Kagiwada ◽  
Dai Chida ◽  
Tomoya Sakatani ◽  
Masahide Asano ◽  
Aya Nambu ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Cyclooxygenase 2 ◽  
Signaling Cascade ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Cox 2 ◽  
The Brain ◽  
Deficient Mice

Abstract IL-1 is an endogenous pyrogen produced upon inflammation or infection. Previously, we showed that, upon injection with turpentine, IL-1 is induced in the brain in association with the development of fever. The role of endogenous IL-1 in the brain and the signaling cascade to activate thermosensitive neurons, however, remain to be elucidated. In this report, febrile response was analyzed after peripheral injection of IL-1α. We found that a normal febrile response was induced even in IL-1α/β-deficient mice, indicating that production of IL-1 in the brain is not necessarily required for the response. In contrast, IL-6-deficient mice did not exhibit a febrile response. Cyclooxygenase (Cox)-2 expression in the brain was strongly induced 1.5 h after injection of IL-1α, whereas IL-6 expression was observed 3 h after the injection. Cox-2 expression in the brain was not influenced by IL-6 deficiency, whereas indomethacin, an inhibitor of cyclooxygenases, completely inhibited induction of IL-6. These observations suggest a mechanism of IL-1-induced febrile response in which IL-1 in the blood activates Cox-2, with the resulting prostaglandin E2 inducing IL-6 in the brain, leading to the development of fever.

scholarly journals Lipopolysaccharide-Induced Fever Depends on Prostaglandin E2 Production Specifically in Brain Endothelial Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4849-4861 ◽  
Author(s):  
Linda Engström ◽  
Johan Ruud ◽  
Anna Eskilsson ◽  
Anders Larsson ◽  
Ludmila Mackerlova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cerebrospinal Fluid ◽  
Prostaglandin E2 ◽  
Hematopoietic Cells ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Brain Endothelial Cells ◽  
Febrile Response ◽  
Pge2 Synthesis ◽  
The Brain

Abstract Immune-induced prostaglandin E2 (PGE2) synthesis is critical for fever and other centrally elicited disease symptoms. The production of PGE2 depends on cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES-1), but the identity of the cells involved has been a matter of controversy. We generated mice expressing mPGES-1 either in cells of hematopoietic or nonhematopoietic origin. Mice lacking mPGES-1 in hematopoietic cells displayed an intact febrile response to lipopolysaccharide, associated with elevated levels of PGE2 in the cerebrospinal fluid. In contrast, mice that expressed mPGES-1 only in hematopoietic cells, although displaying elevated PGE2 levels in plasma but not in the cerebrospinal fluid, showed no febrile response to lipopolysaccharide, thus pointing to the critical role of brain-derived PGE2 for fever. Immunohistochemical stainings showed that induced cyclooxygenase-2 expression in the brain exclusively occurred in endothelial cells, and quantitative PCR analysis on brain cells isolated by flow cytometry demonstrated that mPGES-1 is induced in endothelial cells and not in vascular wall macrophages. Similar analysis on liver cells showed induced expression in macrophages and not in endothelial cells, pointing at the distinct role for brain endothelial cells in PGE2 synthesis. These results identify the brain endothelial cells as the PGE2-producing cells critical for immune-induced fever.

scholarly journals Change in prostaglandin E synthases (PGESs) in microsomal PGES-1 knockout mice in a preterm delivery model

2005 ◽  
Vol 187 (3) ◽  
pp. 339-345 ◽  
Author(s):  
Ken Kubota ◽  
Toshiro Kubota ◽  
Daisuke Kamei ◽  
Makoto Murakami ◽  
Ichiro Kudo ◽  
...  
Keyword(s):  
Preterm Delivery ◽  
Knockout Mice ◽  
Preterm Labor ◽  
Fetal Membrane ◽  
Prostaglandin E ◽  
Wild Type ◽  
Infection And Inflammation ◽  
Mrna And Protein Expression ◽  
Lps Treatment

Most preterm deliveries are associated with infection and inflammation. Prostaglandin E2 (PGE2) is one of the most important mediators in the processes of inflammation, and is converted from PGH2 by various kinds of PGE synthases (PGESs). Among PGESs, microsomal PGES-1 (mPGES-1) is known to be the most important subtype in the processes of inflammation. To evaluate the role of PGESs in preterm delivery, we used mPGES-1 knockout mice in a lipopolysaccharide (LPS)-induced preterm labor model. Unexpectedly, the duration of labor after LPS treatment was not statistically different between C57BL6 wild-type mice and mPGES-1 knockout mice. In wild-type mice, mPGES-1 mRNA and protein expression increased in the myometrium and fetal membrane after LPS treatment. In contrast, the expression of mPGES-2 or cytosolic PGES was not changed by LPS treatment. On mPGES-1 knockout mice, mPGES-2 increased by LPS treatment in myometrium. The present data indicate that mPGES-1 may be involved in LPS-induced preterm labor, but inhibition of mPGES-1 alone may not prevent preterm delivery, because mPGES-2 might compensate for the role of mPGES-1.

scholarly journals mPGES-1 deletion impairs diuretic response to acute water loading

2009 ◽  
Vol 296 (5) ◽  
pp. F1129-F1135 ◽  
Author(s):  
Sunhapas Soodvilai ◽  
Zhanjun Jia ◽  
Mong-Heng Wang ◽  
Zheng Dong ◽  
Tianxin Yang
Keyword(s):  
Prostaglandin E ◽  
Wild Type ◽  
Prostaglandin E Synthase ◽  
Water Load ◽  
Water Loading ◽  
Water Handling ◽  
Diuretic Response ◽  
Established Role ◽  
Stimulation Of

PGE2 has an established role in renal water handling. The present study was undertaken to examine the role of microsomal prostaglandin E synthase-1 (mPGES-1) in the diuretic response to acute and chronic water loading. Compared with wild-type (+/+) controls, mPGES-1 −/− mice exhibited impaired ability to excrete an acute, but not chronic water load. In response to acute water loading, urinary PGE2 excretion in the +/+ mice increased at 2 h, in parallel with increased urine flow. In contrast, the −/− mice exhibited a delayed increase in urinary PGE2 excretion, coinciding with the stimulation of renal medullary mRNA expression of cytosolic prostaglandin E synthase but not mPGES-2. At baseline, renal aquaporin-2 (AQP2) expression in mPGES-1 −/− mice was enhanced compared with the +/+ control. In response to acute water loading, renal AQP2 expression in the +/+ mice was significantly reduced, and this reduction was blunted in the −/− mice. Despite striking changes in AQP2 protein expression, renal AQP2 mRNA in both genotypes largely remained unchanged. Overall, these data support an important role of mPGES-1 in provoking the diuretic response to acute water loading.

Sign in / Sign up

Export Citation Format

Share Document