| Specific and overlapping sphingosine-1-phosphate receptor functions in human synoviocytes: impact of TNF-alpha. | |
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MedLine Citation:
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PMID: 18658144 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sphingosine-1-phosphate (S1P), via interaction with its G protein-coupled receptors, regulates various physiological and pathological responses. The present study investigated the role of S1P/S1P receptor signaling in several functional responses of human fibroblast-like synoviocytes (FLSs) that may contribute to the pathogenesis of rheumatoid arthritis (RA). We report that FLSs express the S1P(1), S1P(2), and S1P(3) receptors. Moreover, exogenously applied S1P induces FLS 1) migration, 2) secretion of inflammatory cytokines/chemokines, and 3) protection from apoptosis. Using specific S1P receptor agonists/antagonists, we determined that S1P stimulates FLS migration through S1P(1) and S1P(3), induces cytokine/chemokine secretion through S1P(2) and S1P(3), and protects from cell apoptosis via S1P(1). The S1P-mediated cell motility and cytokine/chemokine secretion seem to be regulated by the p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK, and Rho kinase signal transduction pathways. Interestingly, treatment of FLSs with tumor necrosis factor-alpha increases S1P(3) expression and correlates with the enhancement of S1P-induced cytokine/chemokine production. Our data suggest that S1P(1), S1P(2), and S1P(3) play essential roles in the pathogenesis of RA by modulating FLS migration, cytokine/chemokine production, and cell survival. Moreover, the cytokine-rich environment of the inflamed synovium may synergize with S1P signaling to exacerbate the clinical manifestations of this autoimmune disease. |
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Authors:
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Chenqi Zhao; Maria J Fernandes; Mélanie Turgeon; Sabrina Tancrède; John Di Battista; Patrice E Poubelle; Sylvain G Bourgoin |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-24 |
Journal Detail:
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Title: Journal of lipid research Volume: 49 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-10-13 Completed Date: 2009-01-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 2323-37 Citation Subset: IM |
Affiliation:
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Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUQ-CHUL, Départements d'Anatomie-Physiologie et Médecine, Faculté de Médecine, Université Laval, Québec, Canada, G1V 4G2. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Arthritis, Rheumatoid
/
etiology,
metabolism,
pathology Cell Movement / physiology Cell Survival / physiology Cells, Cultured Humans Lysophospholipids / metabolism Receptors, Lysosphingolipid / physiology* Sphingosine / analogs & derivatives, metabolism Synovial Fluid / cytology*, metabolism Synovial Membrane / metabolism, pathology Tumor Necrosis Factor-alpha / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Lysophospholipids; 0/Receptors, Lysosphingolipid; 0/S1PR1 protein, human; 0/S1PR2 protein, human; 0/Tumor Necrosis Factor-alpha; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate |
| Comments/Corrections | |
Comment In:
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J Lipid Res. 2008 Nov;49(11):2281-2
[PMID:
18669980
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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