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01-10-2020 | Cytokines | Original Article

Lysophosphatidylinositol, an Endogenous Ligand for G Protein-Coupled Receptor 55, Has Anti-inflammatory Effects in Cultured Microglia

Authors: Tomoki Minamihata, Katsura Takano, Mitsuaki Moriyama, Yoichi Nakamura

Published in: Inflammation | Issue 5/2020

Abstract

Lysophosphatidylinositol (LysoPI), an endogenous ligand for G protein-coupled receptor (GPR) 55, has been known to show various functions in several tissues and cells; however, its roles in the central nervous system (CNS) are not well known. In particular, the detailed effects of LysoPI on microglial inflammatory responses remain unknown. Microglia is the immune cell that has important functions in maintaining immune homeostasis of the CNS. In this study, we explored the effects of LysoPI on inflammatory responses using the mouse microglial cell line BV-2, which was stimulated with lipopolysaccharide (LPS), and some results were confirmed also in rat primary microglia. LysoPI was found to reduce LPS-induced nitric oxide (NO) production and inducible NO synthase protein expression without affecting cell viability in BV-2 cells. LysoPI also suppressed intracellular generation of reactive oxygen species both in BV-2 cells and primary microglia and cytokine release in BV-2 cells. In addition, LysoPI treatment decreased phagocytic activity of LPS-stimulated BV-2 cells and primary microglia. The GPR55 antagonist CID16020046 completely inhibited LysoPI-induced downregulation of phagocytosis in BV-2 microglia, but did not affect the LysoPI-induced decrease in NO production. Our results suggest that LysoPI suppresses microglial phagocytosis via a GPR55-dependent pathway and NO production via a GPR55-independent pathway. LysoPI may contribute to neuroprotection in pathological conditions such as brain injury or neurodegenerative diseases, through its suppressive role in the microglial inflammatory response.

Kreutzberg, G.W. 1996. Microglia: a sensor for pathological events in the CNS. Trends in Neurosciences 19: 312–318. https://doi.org/10.1016/0166-2236(96)10049-7.CrossRefPubMed

Nakamura, Y. 2002. Regulating factors for microglial activation. Biological and Pharmaceutical Bulletin 25: 945–953. https://doi.org/10.1248/bpb.25.945.CrossRefPubMed

Block, M.L., L. Zecca, and J. Hong. 2007. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nature Reviews Neuroscience 8: 57–69. https://doi.org/10.1038/nrn2038.CrossRefPubMed

Neniskyte, U., J.J. Neher, and G.C. Brown. 2011. Neuronal death induced by nanomolar amyloid β is mediated by primary phagocytosis of neurons by microglia. Journal of Biological Chemistry 286: 39904–39913. https://doi.org/10.1074/jbc.M111.267583.CrossRefPubMed

Brown, G.C., and A. Vilalta. 2015. How microglia kill neurons. Brain Research 1628: 288–297. https://doi.org/10.1016/j.brainres.2015.08.031.CrossRefPubMed

Aoki, J., Y. Nagai, H. Hosono, K. Inoue, and H. Arai. 2002. Structure and function of phosphatidylserine-specific phospholipase A1. Biochimica et Biophysica Acta 1582 (1–3): 26–32. https://doi.org/10.1016/s1388-1981(02)00134-8.CrossRefPubMed

Alhouayek, M., J. Masquelier, and G.G. Muccioli. 2018. Lysophosphatidylinositols, from cell membrane constituents to GPR55 ligands. Trends in Pharmacological Sciences 39 (6): 586–604. https://doi.org/10.1016/j.tips.2018.02.011.CrossRefPubMed

Grzelczyk, A., and E. Gendaszewska-Darmach. 2013. Novel bioactive glycerol-based lyosphospholipids: new data ― new insight into their function. Biochimie 95: 667–679. https://doi.org/10.1016/j.biochi.2012.10.009.CrossRefPubMed

Kihara, Y., H. Mizuno, and J. Chun. 2015. Lysophospholipid receptors in drug discovery. Experimental Cell Research 333 (2): 171–177. https://doi.org/10.1016/j.yexcr.2014.11.020.CrossRefPubMed

10.

Zhao, C., M.J. Fernandes, G.D. Prestwich, M. Turgeon, J. Di Battista, T. Clair, P.E. Poubelle, and S.G. Bourgoin. 2008. Regulation of lysophosphatidic acid receptor expression and function in human synoviocytes: implications for rheumatoid arthritis? Molecular Pharmacology 73 (2): 587–600. https://doi.org/10.1124/mol.107.038216.CrossRefPubMed

11.

Bektas, M., M.L. Allende, B.G. Lee, W. Chen, M.J. Amar, A.T. Remaley, J.D. Saba, and R.L. Proia. 2010. Sphingosine 1-phosphate lyase deficiency disrupts lipid homeostasis in liver. Journal of Biological Chemistry 285 (14): 10880–10889. https://doi.org/10.1074/jbc.M109.081489.CrossRefPubMed

12.

Vladykovskaya, E., E. Ozhegov, J.D. Hoetker, Z. Xie, Y. Ahmed, J. Suttles, S. Srivastava, A. Bhatnagar, and O.A. Barski. 2011. Reductive metabolism increases the proinflammatory activity of aldehyde phospholipids. Journal of Lipid Research 52 (12): 2209–2225. https://doi.org/10.1194/jlr.M013854.CrossRefPubMedPubMedCentral

13.

Hung, N.D., M.R. Kim, and D.E. Sok. 2011. 2-Polyunsaturated acyl lysophosphatidylethanolamine attenuates inflammatory response in zymosan A-induced peritonitis in mice. Lipids 46: 893–906. https://doi.org/10.1007/s11745-011-3589-2.CrossRefPubMed

14.

Nishikawa, M., M. Kurano, H. Ikeda, J. Aoki, and Y. Yatomi. 2015. Lysophosphatidylserine has bilateral effects on macrophages in the pathogenesis of atherosclerosis. Journal of Atherosclerosis and Thrombosis 22 (5): 518–526. https://doi.org/10.5551/jat.25650.CrossRefPubMed

15.

Henstridge, C.M., N.A. Balenga, L.A. Ford, R.A. Ross, M. Waldhoer, and A.J. Irving. 2009. The GPR55 ligand L-α-lysophosphatidylinositol promotes RhoA-dependent Ca²⁺ signaling and NFAT activation. FASEB Journal 23 (1): 183–193. https://doi.org/10.1096/fj.08-108670.CrossRefPubMed

16.

Anavi-Goffer, S., G. Baillie, A.J. Irving, J. Gertsch, I.R. Greig, R.G. Pertwee, and R.A. Ross. 2011. Modulation of L-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids. Journal of Biological Chemistry 287 (1): 91–104. https://doi.org/10.1074/jbc.M111.296020.CrossRefPubMed

17.

Frasch, S.C., and D.L. Bratton. 2012. Emerging roles for lysophosphatidylserine in resolution of inflammation. Progress in Lipid Research 51 (3): 199–207. https://doi.org/10.1016/j.plipres.2012.03.001.CrossRefPubMedPubMedCentral

18.

Kamat, S.S., K. Camara, W.H. Parsons, D.H. Chen, M.M. Dix, T.D. Bird, A.R. Howell, and B.F. Cravatt. 2015. Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay. Nature Chemical Biology 11 (2): 164–171. https://doi.org/10.1038/nchembio.1721.CrossRefPubMedPubMedCentral

19.

Wang, X., Y.F. Li, G. Nanayakkara, Y. Shao, B. Liang, L. Cole, W.Y. Yang, X. Li, R. Cueto, J. Yu, H. Wang, and X.F. Yang. 2016. Lysophospholipid receptors, as novel conditional danger receptors and homeostatic receptors modulate inflammation-novel paradigm and therapeutic potential. Journal of Cardiovascular Translational Research 9 (4): 343–359. https://doi.org/10.1007/s12265-016-9700-6.CrossRefPubMedPubMedCentral

20.

Celorrio, M., E. Rojo-Bustamante, D. Fernández-Suárez, E. Sáez, A. Estella-Hermoso de Mendoza, C.E. Müller, M.J. Ramírez, J. Oyarzábal, R. Franco, and M.S. Aymerich. 2017. GPR55: a therapeutic target for Parkinson’s disease? Neuropharmacology 125: 319–332. https://doi.org/10.1016/j.neuropharm.2017.08.017.CrossRefPubMed

21.

Haque, M.E., I.S. Kim, M. Jakaria, M. Akther, and D.K. Choi. 2018. Importance of GPCR-mediated microglial activation in Alzheimer’s disease. Frontiers in Cellular Neuroscience 12: 258. https://doi.org/10.3389/fncel.2018.00258.CrossRefPubMedPubMedCentral

22.

Oka, S., T. Toshida, K. Maruyama, K. Nakajima, A. Yamashita, and T. Sugiura. 2009. 2-Arachidonoyl-sn-glycero-3-phosphoinositol: a possible natural ligand for GPR55. Journal of Biochemistry 145 (1): 13–20. https://doi.org/10.1093/jb/mvn136.CrossRefPubMed

23.

Pietr, M., E. Kozela, R. Levy, N. Rimmerman, Y.H. Lin, N. Stella, Z. Vogel, and A. Juknat. 2009. Differential changes in GPR55 during microglial cell activation. FEBS Letters 583 (12): 2071–2076. https://doi.org/10.1016/j.febslet.2009.05.028.CrossRefPubMed

24.

Kallendrusch, S., S. Kremzow, M. Nowicki, U. Grabiec, R. Winkelmann, A. Benz, and M. Koch. 2013. The G protein-coupled receptor 55 ligand L-α-lysophosphatidylinositol exerts microglia-dependent neuroprotection after excitotoxic lesion. Glia 61 (11): 1822–1831. https://doi.org/10.1002/glia.22560.CrossRefPubMed

25.

Si, Q., Y. Nakamura, and K. Kataoka. 2000. A serum factor enhances production of nitric oxide and tumor necrosis factor-α from cultured microglia. Experimental Neurology 162 (1): 89–97. https://doi.org/10.1006/exnr.2000.7334.CrossRefPubMed

26.

Horvath, R.J., N. Nutile-McMenemy, M.S. Alkaitis, and J.A. Deleo. 2008. Differential migration, LPS-induced cytokine, chemokine, and NO expression in immortalized BV-2 and HAPI cell lines and primary microglial cultures. Journal of Neurochemistry 107 (2): 557–569. https://doi.org/10.1111/j.1471-4159.2008.05633.x.CrossRefPubMedPubMedCentral

27.

de Jong, E.K., A.H. de Haas, N. Brouwer, H.R. van Weering, M. Hensens, I. Bechmann, P. Pratley, E. Wesseling, H.W. Boddeke, and K. Biber. 2008. Expression of CXCL4 in microglia in vitro and in vivo and its possible signaling through CXCR3. Journal of Neurochemistry 105 (5): 1726–1736. https://doi.org/10.1111/j.1471-4159.2008.05267.x.CrossRefPubMed

28.

Kim, Y.L., Y.J. Im, N.C. Ha, and D.S. Im. 2006. Albumin inhibits cytotoxic activity of lysophosphatidylcholine by direct binding. Prostaglandins & Other Lipid Mediators 83 (1-2): 130–138. https://doi.org/10.1016/j.prostaglandins.2006.10.006.CrossRef

29.

Takano, K., K. Sugita, M. Moriyama, K. Hashida, S. Hibino, T. Choshi, R. Murakami, M. Yamada, H. Suzuki, O. Hori, and Y. Nakamura. 2011. A dibenzoylmethane derivative protects against hydrogen peroxide-induced cell death and inhibits lipopolysaccharide-induced nitric oxide production in cultured rat astrocytes. Journal of Neuroscience Research 89: 955–965. https://doi.org/10.1002/jnr.22617.CrossRefPubMed

30.

Bradford, M.M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72 (1–2): 248–254. https://doi.org/10.1006/abio.1976.9999.CrossRefPubMed

31.

Koyama, Y., Y. Kimura, Y. Yoshioka, D. Wakamatsu, R. Kozaki, H. Hashimoto, T. Matsuda, and A. Baba. 2000. Serum-deprivation induces cell death of rat cultured microglia accompanied with expression of Bax protein. Japanese Journal of Pharmacology 83 (4): 351–354. https://doi.org/10.1254/jjp.83.351.CrossRefPubMed

32.

Hsieh, H.L., and C.M. Yang. 2013. Role of redox signaling in neuroinflammation and neurodegenerative diseases. BioMed Research International 2013: 484613–484618. https://doi.org/10.1155/2013/484613.CrossRefPubMedPubMedCentral

33.

Mittal, M., M.R. Siddiqui, K. Tran, S.P. Reddy, and A.B. Malik. 2014. Reactive oxygen species in inflammation and tissue injury. Antioxidants & Redox Signaling 20 (7): 1126–1167. https://doi.org/10.1089/ars.2012.5149.CrossRef

34.

Qin, L., Y. Liu, T. Wang, S.J. Wei, M.L. Block, B. Wilson, B. Liu, and J.S. Hong. 2004. NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. Journal of Biological Chemistry 279 (2): 1415–1421. https://doi.org/10.1074/jbc.M307657200.CrossRefPubMed

35.

Li, B., K. Bedard, S. Sorce, B. Hinz, M. Dubois-Dauphin, and K.H. Krause. 2009. NOX4 expression in human microglia leads to constitutive generation of reactive oxygen species and to constitutive IL-6 expression. Journal of Innate Immunity 1 (6): 570–581. https://doi.org/10.1159/000235563.CrossRefPubMed

36.

Balenga, N.A., E. Aflaki, J. Kargl, W. Platzer, R. Schröder, S. Blättermann, E. Kostenis, A.J. Brown, A. Heinemann, and M. Waldhoer. 2011. GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils. Cell Research 21 (10): 1452–1469. https://doi.org/10.1038/cr.2011.60.CrossRefPubMedPubMedCentral

37.

Li, X., L. Wang, P. Fang, Y. Sun, X. Jiang, H. Wang, and X.F. Yang. 2018. Lysophospholipids induce innate immune transdifferentiation of endothelial cells, resulting in prolonged endothelial activation. Journal of Biological Chemistry 293 (28): 11033–11045. https://doi.org/10.1074/jbc.RA118.002752.CrossRefPubMed

38.

Ginsburg, I., P.A. Ward, and J. Varani. 1989. Lysophosphatides enhance superoxide responses of stimulated human neutrophils. Inflammation 13 (2): 163–174. https://doi.org/10.1007/bf00924787.CrossRefPubMed

39.

Ojala, P.J., T.E. Hirvonen, M. Hermansson, P. Somerharju, and J. Parkkinen. 2007. Acyl chain-dependent effect of lysophosphatidylcholine on human neutrophils. Journal of Leukocyte Biology 82 (6): 1501–1509. https://doi.org/10.1189/jlb.0507292.CrossRefPubMed

40.

Brkić, L., M. Riederer, W.F. Graier, R. Malli, and S. Frank. 2012. Acyl chain-dependent effect of lysophosphatidylcholine on cyclooxygenase (COX)-2 expression in endothelial cells. Atherosclerosis 224 (2): 348–354. https://doi.org/10.1016/j.atherosclerosis.2012.07.038.CrossRefPubMedPubMedCentral

41.

Rao, S.P., M. Riederer, M. Lechleitner, M. Hermansson, G. Desoye, S. Hallström, W.F. Graier, and S. Frank. 2013. Acyl chain-dependent effect of lysophosphatidylcholine on endothelium-dependent vasorelaxation. PLoS One 8 (5): e65155. https://doi.org/10.1371/journal.pone.0065155.CrossRefPubMedPubMedCentral

42.

Tokizane, K., H. Konishi, K. Makide, H. Kawana, S. Nakamuta, K. Kaibuchi, T. Ohwada, J. Aoki, and H. Kiyama. 2017. Phospholipid localization implies microglial morphology and function via Cdc42 in vitro. Glia 65 (5): 740–755. https://doi.org/10.1002/glia.23123.CrossRefPubMed

43.

Ailte, I., A.B. Lingelem, A.S. Kvalvaag, S. Kavaliauskiene, A. Brech, G. Koster, P.G. Dommersnes, J. Bergan, T. Skotland, and K. Sandvig. 2017. Exogenous lysophospholipids with large head groups perturb clathrin-mediated endocytosis. Traffic 18 (3): 176–191. https://doi.org/10.1111/tra.12468.CrossRefPubMed

44.

Amorós, I., A. Barana, R. Caballero, R. Gómez, L. Osuna, M.P. Lillo, J. Tamargo, and E. Delpón. 2010. Endocannabinoids and cannabinoid analogues block human cardiac Kv4.3 channels in a receptor-independent manner. Journal of Molecular and Cellular Cardiology 48 (1): 201–210. https://doi.org/10.1016/j.yjmcc.2009.07.011.CrossRefPubMed

45.

Bondarenko, A., M. Waldeck-Weiermair, S. Naghdi, M. Poteser, R. Malli, and W.F. Graier. 2010. GPR55-dependent and -independent ion signalling in response to lysophosphatidylinositol in endothelial cells. British Journal of Pharmacology 161 (2): 308–320. https://doi.org/10.1111/j.1476-5381.2010.00744.x.CrossRefPubMedPubMedCentral

46.

Bondarenko, A.I., R. Malli, and W.F. Graier. 2011. The GPR55 agonist lysophosphatidylinositol directly activates intermediate-conductance Ca²⁺-activated K⁺ channels. Pflügers Archiv: European Journal of Physiology 462 (2): 245–255. https://doi.org/10.1007/s00424-011-0977-7.CrossRefPubMed

47.

Karpińska, O., M. Baranowska-Kuczko, B. Malinowska, M. Kloza, M. Kusaczuk, A. Gęgotek, P. Golec, I. Kasacka, and H. Kozłowska. 2018. Mechanisms of L-alpha-lysophosphatidylinositol-induced relaxation in human pulmonary arteries. Life Sciences 192: 38–45. https://doi.org/10.1016/j.lfs.2017.11.020.CrossRefPubMed

48.

Kaushal, V., P.D. Koeberle, Y. Wang, and L.C. Schlichter. 2007. The Ca²⁺-activated K⁺ channel KCNN4/KCa3.1 contributes to microglia activation and nitric oxide-dependent neurodegeneration. The Journal of Neuroscience 27 (1): 234–244. https://doi.org/10.1523/JNEUROSCI.3593-06.2007.CrossRefPubMedPubMedCentral

49.

Nguyen, H.M., E.M. Grössinger, M. Horiuchi, K.W. Davis, L.W. Jin, I. Maezawa, and H. Wulff. 2017. Differential Kv1.3, KCa3.1, and Kir2.1 expression in “classically” and “alternatively” activated microglia. Glia 65 (1): 106–121. https://doi.org/10.1002/glia.23078.CrossRefPubMed

50.

Malek, N., K. Popiolek-Barczyk, J. Mika, B. Przewlocka, and K. Starowicz. 2015. Anandamide, acting via CB2 receptors, alleviates LPS-induced neuroinflammation in rat primary microglial cultures. Neural Plasticity 2015: 130639–130610. https://doi.org/10.1155/2015/130639.CrossRefPubMedPubMedCentral

51.

Saliba, S.W., H. Jauch, B. Gargouri, A. Keil, T. Hurrle, N. Volz, F. Mohr, M. van der Stelt, S. Bräse, and B.L. Fiebich. 2018. Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells. Journal of Neuroinflammation 15 (1): 322. https://doi.org/10.1186/s12974-018-1362-7.CrossRefPubMedPubMedCentral

52.

Lieb, K., S. Engels, and B.L. Fiebich. 2003. Inhibition of LPS-induced iNOS and NO synthesis in primary rat microglial cells. Neurochemistry International 42: 131–137. https://doi.org/10.1016/s0197-0186(02)00076-1.CrossRefPubMed

53.

McHugh, D. 2012. GPR18 in microglia: Implications for the CNS and endocannabinoid system signaling. British Journal of Pharmacology 167 (8): 1575–1582. https://doi.org/10.1111/j.1476-5381.2012.02019.x.CrossRefPubMedPubMedCentral

54.

Reyes-Resina, I., G. Navarro, D. Aguinaga, E.I. Canela, C.T. Schoeder, M. Załuski, K. Kieć-Kononowicz, C.A. Saura, C.E. Müller, and R. Franco. 2018. Molecular and functional interaction between GPR18 and cannabinoid CB2 G-protein-coupled receptors. Relevance in neurodegenerative diseases. Biochemical Pharmacology 157: 169–179. https://doi.org/10.1016/j.bcp.2018.06.001.CrossRefPubMed

55.

Fu, R., Q. Shen, P. Xu, J.J. Luo, and Y. Tang. 2014. Phagocytosis of microglia in the central nervous system diseases. Molecular Neurobiology 49 (3): 1422–1434. https://doi.org/10.1007/s12035-013-8620-6.CrossRefPubMedPubMedCentral

56.

Rinne, P., R. Guillamat-Prats, M. Rami, L. Bindila, L. Ring, L.P. Lyytikäinen, E. Raitoharju, N. Oksala, T. Lehtimäki, C. Weber, E.P.C. van der Vorst, and S. Steffens. 2018. Palmitoylethanolamide promotes a proresolving macrophage phenotype and attenuates atherosclerotic plaque formation. Arteriosclerosis, Thrombosis, and Vascular Biology 38 (11): 2562–2575. https://doi.org/10.1161/ATVBAHA.118.311185.CrossRefPubMed

57.

Balenga, N.A., E. Martínez-Pinilla, J. Kargl, R. Schröder, M. Peinhaupt, W. Platzer, Z. Bálint, M. Zamarbide, I.G. Dopeso-Reyes, A. Ricobaraza, J.M. Pérez-Ortiz, E. Kostenis, M. Waldhoer, A. Heinemann, and R. Franco. 2014. Heteromerization of GPR55 and cannabinoid CB2 receptors modulates signalling. British Journal of Pharmacology 171 (23): 5387–5406. https://doi.org/10.1111/bph.12850.CrossRefPubMedPubMedCentral

58.

Moreno, E., C. Andradas, M. Medrano, M.M. Caffarel, E. Pérez-Gómez, S. Blasco-Benito, M. Gómez-Cañas, M.R. Pazos, A.J. Irving, C. Lluís, E.I. Canela, J. Fernández-Ruiz, M. Guzmán, P.J. McCormick, and C. Sánchez. 2014. Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling. Journal of Biological Chemistry 289 (32): 21960–21972. https://doi.org/10.1074/jbc.M114.561761.CrossRefPubMed

59.

Stella, N. 2009. Endocannabinoid signaling in microglial cells. Neuropharmacology 56 Suppl 1: 244–253. https://doi.org/10.1016/j.neuropharm.2008.07.037.CrossRefPubMed

60.

Mecha, M., F.J. Carrillo-Salinas, A. Feliú, L. Mestre, and C. Guaza. 2016. Microglia activation states and cannabinoid system: therapeutic implications. Pharmacology and Therapeutics 166: 40–55. https://doi.org/10.1016/j.pharmthera.2016.06.011.CrossRefPubMed

61.

Hassan, S., K. Eldeeb, P.J. Millns, A.J. Bennett, S.P. Alexander, and D.A. Kendall. 2014. Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation. British Journal of Pharmacology 171 (9): 2426–2439. https://doi.org/10.1111/bph.12615.CrossRefPubMedPubMedCentral

62.

Marichal-Cancino, B.A., A. Fajardo-Valdez, A.E. Ruiz-Contreras, M. Mendez-Díaz, and O. Prospero-García. 2017. Advances in the physiology of GPR55 in the central nervous system. Current Neuropharmacology 15 (5): 771–778. https://doi.org/10.2174/1570159X14666160729155441.CrossRefPubMed

63.

Cooper, C.L., G.H. Jeohn, P. Tobias, and J.S. Hong. 2002. Serum-dependence of LPS-induced neurotoxicity in rat cortical neurons. Annals of the New York Academy of Sciences 962: 306–317. https://doi.org/10.1111/j.1749-6632.2002.tb04076.x.CrossRefPubMed

64.

McHugh, D., S.S. Hu, N. Rimmerman, A. Juknat, Z. Vogel, J.M. Walker, and H.B. Bradshaw. 2010. N-Arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neuroscience 11: 44. https://doi.org/10.1186/1471-2202-11-44.CrossRefPubMedPubMedCentral

65.

Plastira, I., E. Bernhart, M. Goeritzer, H. Reicher, V.B. Kumble, N. Kogelnik, A. Wintersperger, A. Hammer, S. Schlager, K. Jandl, A. Heinemann, D. Kratky, E. Malle, and W. Sattler. 2016. 1-Oleyl-lysophosphatidic acid (LPA) promotes polarization of BV-2 and primary murine microglia towards an M1-like phenotype. Journal of Neuroinflammation 13 (1): 205. https://doi.org/10.1186/s12974-016-0701-9.CrossRefPubMedPubMedCentral

66.

Hill, J.D., V. Zuluaga-Ramirez, S. Gajghate, M. Winfield, and Y. Persidsky. 2018. Activation of GPR55 increases neural stem cell proliferation and promotes early adult hippocampal neurogenesis. British Journal of Pharmacology 175 (16): 3407–3421. https://doi.org/10.1111/bph.14387.CrossRefPubMedPubMedCentral

67.

Hill, J.D., V. Zuluaga-Ramirez, S. Gajghate, M. Winfield, U. Sriram, S. Rom, and Y. Persidsky. 2019. Activation of GPR55 induces neuroprotection of hippocampal neurogenesis and immune responses of neural stem cells following chronic, systemic inflammation. Brain, Behavior, and Immunity 76: 165–181. https://doi.org/10.1016/j.bbi.2018.11.017.CrossRefPubMed

68.

Stančić, A., K. Jandl, C. Hasenöhrl, F. Reichmann, G. Marsche, R. Schuligoi, A. Heinemann, M. Storr, and R. Schicho. 2015. The GPR55 antagonist CID16020046 protects against intestinal inflammation. Neurogastroenterology and Motility 27 (10): 1432–1445. https://doi.org/10.1111/nmo.12639.CrossRefPubMedPubMedCentral

69.

Brown, A.J., I. Castellano-Pellicena, C.P. Haslam, P.L. Nichols, and S.J. Dowell. 2018. Structure-activity relationship of the GPR55 antagonist, CID16020046. Pharmacology 102 (5–6): 324–331. https://doi.org/10.1159/000493490.CrossRefPubMed

70.

Janefjord, E., J.L. Mååg, B.S. Harvey, and S.D. Smid. 2014. Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cellular and Molecular Neurobiology 34 (1): 31–42. https://doi.org/10.1007/s10571-013-9984-x.CrossRefPubMed

71.

Li, K., J.Y. Feng, Y.Y. Li, B. Yuece, X.H. Lin, L.Y. Yu, Y.N. Li, Y.J. Feng, and M. Storr. 2013. Anti-inflammatory role of cannabidiol and O-1602 in cerulein-induced acute pancreatitis in mice. Pancreas 42 (1): 123–129. https://doi.org/10.1097/MPA.0b013e318259f6f0.CrossRefPubMed

72.

Wei, D., H. Wang, J. Yang, Z. Dai, R. Yang, S. Meng, Y. Li, and X. Lin. 2020. Effects of O-1602 and CBD on TNBS-induced colonic disturbances. Neurogastroenterology and Motility 32 (3): e13756. https://doi.org/10.1111/nmo.13756.CrossRefPubMed

Title: Lysophosphatidylinositol, an Endogenous Ligand for G Protein-Coupled Receptor 55, Has Anti-inflammatory Effects in Cultured Microglia
Authors: Tomoki Minamihata
Katsura Takano
Mitsuaki Moriyama
Yoichi Nakamura
Publication date: 01-10-2020
Publisher: Springer US
Keyword: Cytokines
Published in: Inflammation / Issue 5/2020
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-020-01271-4

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Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Lysophosphatidylinositol, an Endogenous Ligand for G Protein-Coupled Receptor 55, Has Anti-inflammatory Effects in Cultured Microglia

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

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» View more highlights on the ACC 2024 congress hub page