Lysoglycerophospholipids in chronic inflammatory disorders: The PLA2/LPC and ATX/LPA axes |
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| Authors: | Ioanna Sevastou Eleanna KaffeMarios-Angelos Mouratis Vassilis Aidinis |
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| Affiliation: | Institute of Immunology, Biomedical Sciences Research Center “Alexander Fleming”, 34 Fleming Street, 16672 Athens, Greece |
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| Abstract: | Lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), the most prominent lysoglycerophospholipids, are emerging as a novel class of inflammatory lipids, joining thromboxanes, leukotrienes and prostaglandins with which they share metabolic pathways and regulatory mechanisms. Enzymes that participate in LPC and LPA metabolism, such as the phospholipase A2 superfamily (PLA2) and autotaxin (ATX, ENPP2), play central roles in regulating LPC and LPA levels and consequently their actions. LPC/LPA biosynthetic pathways will be briefly presented and LPC/LPA signaling properties and their possible functions in the regulation of the immune system and chronic inflammation will be reviewed. Furthermore, implications of exacerbated LPC and/or LPA signaling in the context of chronic inflammatory diseases, namely rheumatoid arthritis, multiple sclerosis, pulmonary fibrosis and hepatitis, will be discussed. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. |
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| Keywords: | AA, arachidonic acid AIH, autoimmune hepatitis ATX, autotaxin BALF, bronchoalveolar fluid BLM, Bleomycin C1P, ceramide 1-phosphate CFA, cryptogenic fibrosing alveolitis CNS, central nervous system COX-2, cyclooxygenase type 2 cPA, cyclic phosphatidic acid cPLA2, cytosolic PLA2 CSF, cerebrospinal fluid DCs, dendritic cells DPPC, dipalmitoyl phosphatidyl choline EAE, experimental autoimmune encephalomyelitis ECs, endothelial cells ET-1, endothelin-1 HB-EGF, heparin-binding epidermal growth factor-like growth factor hBMSCs, human bone marrow-derived mesenchymal stem cells HBV, hepatitis B Virus HCAECs, human coronary artery endothelial cells HCC, hepatitis-related hepatocellular cancer HCV, hepatitis C Virus HDL, high density lipoprotein HEVs, high endothelial venules HMGB1, high-mobility group box 1 HUVECs, human umbellical vein endothelial cells ICAM-1, intracellular adhesion molecule-1 IL-1β, interleukin-1β iNKTs, invariant NKT cells IPF, idiopathic pulmonary fibrosis iPLA2, calcium-independent PLA2 LCAT, lecithin-cholesterol-acyl-transferase LPA, lysophosphatidic acid LPC, Lysophosphatidylcholine LPCAT, lysophosphatidylcholine acyltransferase LPP, lipid-phosphate phosphatase Lp-PLA2, lipoprotein-associated PLA2 lysoPLD, lysophospholipase D MCP-1, monocyte chemotactic protein-1 MIP-2, macrophage inflammatory protein &minus 2 MS, multiple sclerosis NASH, non-alcoholic steatohepatitis NKT, natural killer T OA, osteoarthritis oxLDL, oxidized low density lipoprotein PA, phosphatidic acid PAF, platelet activating factor PBC, primary billiary cirrhosis PBM, peripheral blood monocyte PC, phosphatidylcholine PE, phosphatidylethanolamine PEMT, PE-N-ethyltransferase PI3, phosphatidylinositol 3 PKC, protein kinase C PLA2, phospholipase A2 PMN, peripheral blood polymorphonuclear leukocyte PPARγ, peroxisome proliferator-activated receptor γ PUFA, polyunsaturated fatty acid RA, rheumatoid arthritis ROS, reactive oxygen species S1P, sphingosine 1-phosphate SDF-1, stromal cell-derived factor-1 SF, synovial fibroblast SMCs, smooth muscle cells SPC, sphingosylphosphorylcholine sPLA2, secreted PLA2 SPs, surfactant proteins VCAM-1, vascular cell adhesion molecule-1 VEGF, vascular endothelial growth factor |
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