A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis.
Rheumatoid arthritis (RA) is a destructive arthropathy with systemic manifestations, characterized by chronic synovial inflammation. Under the influence of the pro-inflammatory milieu synovial fibroblasts (SFs), the main effector cells in disease pathogenesis become activated and hyperplastic while...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3726599?pdf=render |
| _version_ | 1818131751662256128 |
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| author | Ioanna Nikitopoulou Eleanna Kaffe Ioanna Sevastou Ivi Sirioti Martina Samiotaki Damian Madan Glenn D Prestwich Vassilis Aidinis |
| author_facet | Ioanna Nikitopoulou Eleanna Kaffe Ioanna Sevastou Ivi Sirioti Martina Samiotaki Damian Madan Glenn D Prestwich Vassilis Aidinis |
| author_sort | Ioanna Nikitopoulou |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a destructive arthropathy with systemic manifestations, characterized by chronic synovial inflammation. Under the influence of the pro-inflammatory milieu synovial fibroblasts (SFs), the main effector cells in disease pathogenesis become activated and hyperplastic while releasing a number of signals that include pro-inflammatory factors and tissue remodeling enzymes. Activated RA SFs in mouse or human arthritic joints express significant quantities of autotaxin (ATX), a lysophospholipase D responsible for the majority of lysophosphatidic acid (LPA) production in the serum and inflamed sites. Conditional genetic ablation of ATX from SFs resulted in attenuation of disease symptoms in animal models, an effect attributed to diminished LPA signaling in the synovium, shown to activate SF effector functions. Here we show that administration of 1-bromo-3(S)-hydroxy-4-(palmitoyloxy)butyl-phosphonate (BrP-LPA), a metabolically stabilized analog of LPA and a dual function inhibitor of ATX and pan-antagonist of LPA receptors, attenuates collagen induced arthritis (CIA) development, thus validating the ATX/LPA axis as a novel therapeutic target in RA. |
| first_indexed | 2024-12-11T08:25:55Z |
| format | Article |
| id | doaj.art-b5ec6ff582fd49969c668417ad1c6abb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T08:25:55Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b5ec6ff582fd49969c668417ad1c6abb2022-12-22T01:14:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e7094110.1371/journal.pone.0070941A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis.Ioanna NikitopoulouEleanna KaffeIoanna SevastouIvi SiriotiMartina SamiotakiDamian MadanGlenn D PrestwichVassilis AidinisRheumatoid arthritis (RA) is a destructive arthropathy with systemic manifestations, characterized by chronic synovial inflammation. Under the influence of the pro-inflammatory milieu synovial fibroblasts (SFs), the main effector cells in disease pathogenesis become activated and hyperplastic while releasing a number of signals that include pro-inflammatory factors and tissue remodeling enzymes. Activated RA SFs in mouse or human arthritic joints express significant quantities of autotaxin (ATX), a lysophospholipase D responsible for the majority of lysophosphatidic acid (LPA) production in the serum and inflamed sites. Conditional genetic ablation of ATX from SFs resulted in attenuation of disease symptoms in animal models, an effect attributed to diminished LPA signaling in the synovium, shown to activate SF effector functions. Here we show that administration of 1-bromo-3(S)-hydroxy-4-(palmitoyloxy)butyl-phosphonate (BrP-LPA), a metabolically stabilized analog of LPA and a dual function inhibitor of ATX and pan-antagonist of LPA receptors, attenuates collagen induced arthritis (CIA) development, thus validating the ATX/LPA axis as a novel therapeutic target in RA.http://europepmc.org/articles/PMC3726599?pdf=render |
| spellingShingle | Ioanna Nikitopoulou Eleanna Kaffe Ioanna Sevastou Ivi Sirioti Martina Samiotaki Damian Madan Glenn D Prestwich Vassilis Aidinis A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis. PLoS ONE |
| title | A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis. |
| title_full | A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis. |
| title_fullStr | A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis. |
| title_full_unstemmed | A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis. |
| title_short | A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis. |
| title_sort | metabolically stabilized phosphonate analog of lysophosphatidic acid attenuates collagen induced arthritis |
| url | http://europepmc.org/articles/PMC3726599?pdf=render |
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