Phospholipase A1 Member A Activates Fibroblast-like Synoviocytes through the Autotaxin-Lysophosphatidic Acid Receptor Axis
Lysophosphatidylserine (lysoPS) is known to regulate immune cell functions. Phospholipase A1 member A (PLA1A) can generate this bioactive lipid through hydrolysis of sn-1 fatty acids on phosphatidylserine (PS). PLA1A has been associated with cancer metastasis, asthma, as well as acute coronary syndr...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12685 |
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| author | Yang Zhao Stephan Hasse Myriam Vaillancourt Chenqi Zhao Lynn Davis Eric Boilard Paul Fortin John Di Battista Patrice E. Poubelle Sylvain G. Bourgoin |
| author_facet | Yang Zhao Stephan Hasse Myriam Vaillancourt Chenqi Zhao Lynn Davis Eric Boilard Paul Fortin John Di Battista Patrice E. Poubelle Sylvain G. Bourgoin |
| author_sort | Yang Zhao |
| collection | DOAJ |
| description | Lysophosphatidylserine (lysoPS) is known to regulate immune cell functions. Phospholipase A1 member A (PLA1A) can generate this bioactive lipid through hydrolysis of sn-1 fatty acids on phosphatidylserine (PS). PLA1A has been associated with cancer metastasis, asthma, as well as acute coronary syndrome. However, the functions of PLA1A in the development of systemic autoimmune rheumatic diseases remain elusive. To investigate the possible implication of PLA1A during rheumatic diseases, we monitored PLA1A in synovial fluids from patients with rheumatoid arthritis and plasma of early-diagnosed arthritis (EA) patients and clinically stable systemic lupus erythematosus (SLE) patients. We used human primary fibroblast-like synoviocytes (FLSs) to evaluate the PLA1A-induced biological responses. Our results highlighted that the plasma concentrations of PLA1A in EA and SLE patients were elevated compared to healthy donors. High concentrations of PLA1A were also detected in synovial fluids from rheumatoid arthritis patients compared to those from osteoarthritis (OA) and gout patients. The origin of PLA1A in FLSs and the arthritic joints remained unknown, as healthy human primary FLSs does not express the PLA1A transcript. Besides, the addition of recombinant PLA1A stimulated cultured human primary FLSs to secrete IL-8. Preincubation with heparin, autotaxin (ATX) inhibitor HA130 or lysophosphatidic acid (LPA) receptor antagonist Ki16425 reduced PLA1A-induced-secretion of IL-8. Our data suggested that FLS-associated PLA1A cleaves membrane-exposed PS into lysoPS, which is subsequently converted to LPA by ATX. Since primary FLSs do not express any lysoPS receptors, the data suggested PLA1A-mediated pro-inflammatory responses through the ATX-LPA receptor signaling axis. |
| first_indexed | 2024-03-10T04:53:35Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:53:35Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b65a1cf4393f452dbf137037cd027a6b2023-11-23T02:26:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231268510.3390/ijms222312685Phospholipase A1 Member A Activates Fibroblast-like Synoviocytes through the Autotaxin-Lysophosphatidic Acid Receptor AxisYang Zhao0Stephan Hasse1Myriam Vaillancourt2Chenqi Zhao3Lynn Davis4Eric Boilard5Paul Fortin6John Di Battista7Patrice E. Poubelle8Sylvain G. Bourgoin9Centre de Recherche du CHU de Québec, Université Laval, Québec, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec, Université Laval, Québec, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec, Université Laval, Québec, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec, Université Laval, Québec, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec, Université Laval, Québec, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec, Université Laval, Québec, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec, Université Laval, Québec, QC G1V 4G2, CanadaDepartment of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montréal, QC H3G 2M1, CanadaCentre de Recherche du CHU de Québec, Université Laval, Québec, QC G1V 4G2, CanadaCentre de Recherche du CHU de Québec, Université Laval, Québec, QC G1V 4G2, CanadaLysophosphatidylserine (lysoPS) is known to regulate immune cell functions. Phospholipase A1 member A (PLA1A) can generate this bioactive lipid through hydrolysis of sn-1 fatty acids on phosphatidylserine (PS). PLA1A has been associated with cancer metastasis, asthma, as well as acute coronary syndrome. However, the functions of PLA1A in the development of systemic autoimmune rheumatic diseases remain elusive. To investigate the possible implication of PLA1A during rheumatic diseases, we monitored PLA1A in synovial fluids from patients with rheumatoid arthritis and plasma of early-diagnosed arthritis (EA) patients and clinically stable systemic lupus erythematosus (SLE) patients. We used human primary fibroblast-like synoviocytes (FLSs) to evaluate the PLA1A-induced biological responses. Our results highlighted that the plasma concentrations of PLA1A in EA and SLE patients were elevated compared to healthy donors. High concentrations of PLA1A were also detected in synovial fluids from rheumatoid arthritis patients compared to those from osteoarthritis (OA) and gout patients. The origin of PLA1A in FLSs and the arthritic joints remained unknown, as healthy human primary FLSs does not express the PLA1A transcript. Besides, the addition of recombinant PLA1A stimulated cultured human primary FLSs to secrete IL-8. Preincubation with heparin, autotaxin (ATX) inhibitor HA130 or lysophosphatidic acid (LPA) receptor antagonist Ki16425 reduced PLA1A-induced-secretion of IL-8. Our data suggested that FLS-associated PLA1A cleaves membrane-exposed PS into lysoPS, which is subsequently converted to LPA by ATX. Since primary FLSs do not express any lysoPS receptors, the data suggested PLA1A-mediated pro-inflammatory responses through the ATX-LPA receptor signaling axis.https://www.mdpi.com/1422-0067/22/23/12685phosphatidylserine-specific phospholipase A1lyso-phospholipidlysophosphatidic acidlyso-phosphatidylserineautotaxinchemokines |
| spellingShingle | Yang Zhao Stephan Hasse Myriam Vaillancourt Chenqi Zhao Lynn Davis Eric Boilard Paul Fortin John Di Battista Patrice E. Poubelle Sylvain G. Bourgoin Phospholipase A1 Member A Activates Fibroblast-like Synoviocytes through the Autotaxin-Lysophosphatidic Acid Receptor Axis International Journal of Molecular Sciences phosphatidylserine-specific phospholipase A1 lyso-phospholipid lysophosphatidic acid lyso-phosphatidylserine autotaxin chemokines |
| title | Phospholipase A1 Member A Activates Fibroblast-like Synoviocytes through the Autotaxin-Lysophosphatidic Acid Receptor Axis |
| title_full | Phospholipase A1 Member A Activates Fibroblast-like Synoviocytes through the Autotaxin-Lysophosphatidic Acid Receptor Axis |
| title_fullStr | Phospholipase A1 Member A Activates Fibroblast-like Synoviocytes through the Autotaxin-Lysophosphatidic Acid Receptor Axis |
| title_full_unstemmed | Phospholipase A1 Member A Activates Fibroblast-like Synoviocytes through the Autotaxin-Lysophosphatidic Acid Receptor Axis |
| title_short | Phospholipase A1 Member A Activates Fibroblast-like Synoviocytes through the Autotaxin-Lysophosphatidic Acid Receptor Axis |
| title_sort | phospholipase a1 member a activates fibroblast like synoviocytes through the autotaxin lysophosphatidic acid receptor axis |
| topic | phosphatidylserine-specific phospholipase A1 lyso-phospholipid lysophosphatidic acid lyso-phosphatidylserine autotaxin chemokines |
| url | https://www.mdpi.com/1422-0067/22/23/12685 |
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