Endocannabinoid hydrolysis inhibition unmasks that unsaturated fatty acids induce a robust biosynthesis of 2-arachidonoyl-glycerol and its congeners in human myeloid leukocytes
© 2020 The Authors. The FASEB Journal published by Wiley Periodicals, Inc. on behalf of Federation of American Societies for Experimental Biology..
The endocannabinoid (eCB) 2-arachidonoyl-gycerol (2-AG) modulates immune responses by activating cannabinoid receptors or through its multiple metabolites, notably eicosanoids. Thus, 2-AG hydrolysis inhibition might represent an interesting anti-inflammatory strategy that would simultaneously increase the levels of 2-AG and decrease those of eicosanoids. Accordingly, 2-AG hydrolysis inhibition increased 2-AG half-life in neutrophils. Under such setting, neutrophils, eosinophils, and monocytes synthesized large amounts of 2-AG and other monoacylglycerols (MAGs) in response to arachidonic acid (AA) and other unsaturated fatty acids (UFAs). Arachidonic acid and UFAs were ~1000-fold more potent than G protein-coupled receptor (GPCR) agonists. Triascin C and thimerosal, which, respectively, inhibit fatty acyl-CoA synthases and acyl-CoA transferases, prevented the UFA-induced MAG biosynthesis, implying glycerolipid remodeling. 2-AG and other MAG biosynthesis was preceded by that of the corresponding lysophosphatidic acid (LPA). However, we could not directly implicate LPA dephosphorylation in MAG biosynthesis. While GPCR agonists poorly induced 2-AG biosynthesis, they inhibited that induced by AA by 25%-50%, suggesting that 2-AG biosynthesis is decreased when leukocytes are surrounded by a pro-inflammatory entourage. Our data strongly indicate that human leukocytes use AA and UFAs to biosynthesize biologically significant concentrations of 2-AG and other MAGs and that hijacking the immune system with 2-AG hydrolysis inhibitors might diminish inflammation in humans.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 34(2020), 3 vom: 01. März, Seite 4253-4265 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Turcotte, Caroline [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.01.2021 Date Revised 21.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1096/fj.201902916R |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM306079364 |
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| 100 | 1 | |a Turcotte, Caroline |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Endocannabinoid hydrolysis inhibition unmasks that unsaturated fatty acids induce a robust biosynthesis of 2-arachidonoyl-glycerol and its congeners in human myeloid leukocytes |
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| 500 | |a Date Completed 21.01.2021 | ||
| 500 | |a Date Revised 21.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Authors. The FASEB Journal published by Wiley Periodicals, Inc. on behalf of Federation of American Societies for Experimental Biology. | ||
| 520 | |a The endocannabinoid (eCB) 2-arachidonoyl-gycerol (2-AG) modulates immune responses by activating cannabinoid receptors or through its multiple metabolites, notably eicosanoids. Thus, 2-AG hydrolysis inhibition might represent an interesting anti-inflammatory strategy that would simultaneously increase the levels of 2-AG and decrease those of eicosanoids. Accordingly, 2-AG hydrolysis inhibition increased 2-AG half-life in neutrophils. Under such setting, neutrophils, eosinophils, and monocytes synthesized large amounts of 2-AG and other monoacylglycerols (MAGs) in response to arachidonic acid (AA) and other unsaturated fatty acids (UFAs). Arachidonic acid and UFAs were ~1000-fold more potent than G protein-coupled receptor (GPCR) agonists. Triascin C and thimerosal, which, respectively, inhibit fatty acyl-CoA synthases and acyl-CoA transferases, prevented the UFA-induced MAG biosynthesis, implying glycerolipid remodeling. 2-AG and other MAG biosynthesis was preceded by that of the corresponding lysophosphatidic acid (LPA). However, we could not directly implicate LPA dephosphorylation in MAG biosynthesis. While GPCR agonists poorly induced 2-AG biosynthesis, they inhibited that induced by AA by 25%-50%, suggesting that 2-AG biosynthesis is decreased when leukocytes are surrounded by a pro-inflammatory entourage. Our data strongly indicate that human leukocytes use AA and UFAs to biosynthesize biologically significant concentrations of 2-AG and other MAGs and that hijacking the immune system with 2-AG hydrolysis inhibitors might diminish inflammation in humans | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CB2 receptor | |
| 650 | 4 | |a Inflammation | |
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| 650 | 4 | |a MAFP | |
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| 650 | 7 | |a Arachidonic Acids |2 NLM | |
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| 700 | 1 | |a Archambault, Anne-Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Dumais, Élizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Cyril |e verfasserin |4 aut | |
| 700 | 1 | |a Blanchet, Marie-Renée |e verfasserin |4 aut | |
| 700 | 1 | |a Bissonnette, Elyse |e verfasserin |4 aut | |
| 700 | 1 | |a Ohashi, Nami |e verfasserin |4 aut | |
| 700 | 1 | |a Yamamoto, Keiko |e verfasserin |4 aut | |
| 700 | 1 | |a Itoh, Toshimasa |e verfasserin |4 aut | |
| 700 | 1 | |a Laviolette, Michel |e verfasserin |4 aut | |
| 700 | 1 | |a Veilleux, Alain |e verfasserin |4 aut | |
| 700 | 1 | |a Boulet, Louis-Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Di Marzo, Vincenzo |e verfasserin |4 aut | |
| 700 | 1 | |a Flamand, Nicolas |e verfasserin |4 aut | |
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