Dual phase regulation of experimental allergic encephalomyelitis by platelet-activating factor

Kihara, Yasuyuki; Ishii, Satoshi; Kita, Yoshiaki; Toda, Akiko; Shimada, Atsuyoshi; Shimizu, Takao

doi:10.1084/jem.20050660

Cited by 75 publications

(64 citation statements)

References 62 publications

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“…We previously reported that PAF exacerbates inflammation in the chronic phase of EAE by the enhancement of phagocytosis in microglia/macrophages and subsequent production of TNF-␣ (19). Furthermore, there was a strong correlation between PAF levels and clinical scores of EAE (13,19). However, in the current study, no eicosanoid was correlated with the clinical scores of EAE.…”

Section: Aa Cascade-targeted Transcriptomics Imply That Aa Cascade Playscontrasting

confidence: 49%

Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis

Kihara

Matsushita

Kita

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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123

107

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The arachidonic acid (AA) cascade produces eicosanoids, such as prostaglandins (PGs), that regulate physiological and pathological functions. Although various nonsteroidal anti-inflammatory drugs have been developed, blocking upstream components (cyclooxygenase-1 and -2) of the AA cascade leads to severe side effects, including gastrointestinal ulcers and cardiovascular events, respectively, due to the complexity of the AA cascade. Here, using an AA cascade-targeted lipidomics approach, we report that microsomal PGE synthase 1 (mPGES-1) plays a key role in experimental autoimmune encephalomyelitis (EAE). Eicosanoids (mainly PGD 2) are produced constitutively in the spinal cord of naive mice. However, in EAE lesions, the PGE 2 pathway is favored and the PGD2, PGI2, and 5-lipoxygenase pathways are attenuated. Furthermore, mPGES-1 ؊/؊ mice showed less severe symptoms of EAE and lower production of IL-17 and IFN-␥ than mPGES-1 ؉/؉ mice. Expression of PGE2 receptors (EP1, EP2, and EP4) was elevated in EAE lesions and correlated with clinical symptoms. Immunohistochemistry on central nervous systems of EAE mice and multiple sclerosis (MS) patients revealed overt expression of mPGES-1 protein in microglia/macrophages. Thus, the mPGES-1-PGE 2-EPs axis of the AA cascade may exacerbate EAE pathology. Our findings have important implications for the design of therapies for MS.autoimmunity ͉ demyelination ͉ lipid mediator ͉ mass spectrometry ͉ Th17

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Section: Aa Cascade-targeted Transcriptomics Imply That Aa Cascade Playscontrasting

confidence: 49%

Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis

Kihara

Matsushita

Kita

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

123

107

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“…However, 56-5 which fails to stimulate IL-1β release in U937 macrophage-like cells, increases disease progression in the EAE model. This action of 56-5 might be related to its chemical similarity with platelet activating factor, which also has a role in multiple sclerosis (Kihara et al 2005).…”

Section: Lipopolysaccharide (Lps) Is An Example Of a Pamp That Can Bimentioning

confidence: 99%

“…Indeed, PAF levels and PAF receptor mRNA expression in the spinal cord are correlated with the EAE disease progression. Moreover, PAF receptor knockout mice exhibit a lower incidence and less severe symptoms in the chronic phase of EAE compared with WT mice (Kihara et al 2005). In addition, macrophages from PAF receptor knockout mice exhibit enhanced phagocytic activity and TNF-α production.…”

Section: Effect Of 56-5 and 77-6 On Disease Progression In Eae--sincementioning

confidence: 99%

Effect of ether glycerol lipids on interleukin-1β release and experimental autoimmune encephalomyelitis

Boomkamp

Byun

Ubhi

et al. 2016

Chemistry and Physics of Lipids

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This version is available at https://strathprints.strath.ac.uk/54188/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. ABSTRACT--We have assessed the effect of two ether glycerol lipids, 77-6 ((2S, 3R)-4-(Tetradecyloxy)-2-amino-1,3-butanediol) and 56-5 ((S)-2-Amino-3-O-hexadecyl-1-propanol), which are substrates for sphingosine kinases, on inflammatory responses. Treatment of differentiated U937 macrophage-like cells with 77-6 but not 56-5 enhanced IL-1β release; either alone or in the presence of LPS. The stimulatory effect of sphingosine or 77-6 on LPSstimulated IL-1β release was reduced by pretreatment of cells with the caspase-1 inhibitor, Ac-YVAD-CHO, thereby indicating a role for the inflammasome. The enhancement of LPSstimulated IL-1β release in response to sphingosine, but not 77-6, was reduced by pretreatment of cells with the cathepsin B inhibitor, CA074Me, indicating a role for lysosomal destabilization in the effect of sphingosine. Administration of 56-5 to mice increased disease progression in an experimental autoimmune encephalomyelitis model and this was associated with a considerable increase in the infiltration of CD4 + T-cells, CD11b + monocytes and F4/80 + macrophages in the spinal cord. 56-5 and 77-6 were without effect on the degradation of myc-tagged sphingosine 1-phosphate 1 receptor in CCL39 cells. Therefore, the effect of 56-5 on EAE disease progression is likely to be independent of the inflammasome or the sphingosine 1-phosphate 1 receptor. However, 56-5 is chemically similar to platelet activating factor and the exacerbation of EAE disease progression might be linked to platelet activating factor receptor signaling.

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“…Biosynthesis of PAF involves production of 1-O-alkyl-lysophosphatidylcholine (LPC) by PLa 2 , followed by its acetylation by LPC acyltransferase 2 (LPCaT2) [70]. analyses of PaF receptor (PaFr)-deficient mice have revealed important roles for this particular lipid mediator in inflammation and allergy [21,29,54]. Since PaFr also recognizes PaF-like oxidized phospholipids [71], some of the implied biological actions of PaF might actually be ascribed to some oxidized phospholipids.…”

Section: Class 2: Lysophosholipids and Their Derivativesmentioning

confidence: 99%

Lipid Mediators in Life Science

2011

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"Lipid mediators" represent a class of bioactive lipids that are produced locally through specific biosynthetic pathways in response to extracellular stimuli. They are exported extracellularly, bind to their cognate G protein-coupled receptors (GPCRs) to transmit signals to target cells, and are then sequestered rapidly through specific enzymatic or non-enzymatic processes. Because of these properties, lipid mediators can be regarded as local hormones or autacoids. Unlike proteins, whose information can be readily obtained from the genome, we cannot directly read out the information of lipids from the genome since they are not genome-encoded. However, we can indirectly follow up the dynamics and functions of lipid mediators by manipulating the genes encoding a particular set of proteins that are essential for their biosynthesis (enzymes), transport (transporters), and signal transduction (receptors). Lipid mediators are involved in many physiological processes, and their dysregulations have been often linked to various diseases such as inflammation, infertility, atherosclerosis, ischemia, metabolic syndrome, and cancer. In this article, I will give an overview of the basic knowledge of various lipid mediators, and then provide an example of how research using mice, gene-manipulated for a lipid mediator-biosynthetic enzyme, contributes to life science and clinical applications.

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Dual phase regulation of experimental allergic encephalomyelitis by platelet-activating factor

Cited by 75 publications

References 62 publications

Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis

Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis

Effect of ether glycerol lipids on interleukin-1β release and experimental autoimmune encephalomyelitis

Lipid Mediators in Life Science

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