Premium
Lysophosphatidic acid and its receptors in the pathogenesis of rheumatoid arthritis
Author(s) -
Zhao Chenqi,
Fernandes Maria,
Poubelle Patrice,
Bourgoin Sylvain
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a113-a
Subject(s) - lysophosphatidic acid , autotaxin , receptor , proinflammatory cytokine , pathogenesis , inflammation , cytokine , g protein coupled receptor , chemokine , chemotaxis , microbiology and biotechnology , cancer research , chemistry , immunology , biology , medicine
Background Lysophosphatidic acid (LPA) is a bioactive lipid mediator that plays a central role in a broad ranges of physiological and pathological processes, through activating its G‐protein coupled receptors. It is worth noting that Autotaxin (ATX), an enzyme that produces the major part of extracellular LPA, is expressed at significantly higher levels in synoviocytes from patients with rheumatoid arthritis (RA). Whereas LPA was implicated in human tumorigenesis the RA synovium resemble the tumor phenotype with many features. Thus it is possible that LPA, via interacting with its receptors, plays a potential role in the pathogenesis of RA. Results We firstly discovered that the receptors for LPA, namely LPA1, LPA2, and LPA3, are all expressed in human synoviocytes; and the expression of LPA3 by synoviocytes is up‐regulated by the proinflammatory cytokine, TNF‐α. Our data also showed that exogenously applied LPA could stimulate the production of IL‐8 by synoviocytes, an important neutrophil chemotactic factor that can recruit inflammatory leucocytes to the inflammation sites. Finally, antagonists of LPA receptors, VPC32183, significantly inhibited LPA‐induced production of IL‐8. Conclusions These findings suggest that LPA, through the interaction with its receptors, would contribute to the pathogenesis of RA by stimulating inflammatory chemokine IL‐8. Our results provide novel insights into the expression of functional LPA receptors in synoviocytes. Since LPA receptor antagonists efficiently down‐regulate LPA‐mediated IL‐8 protein expression, the blockade of LPA receptor may offer potential for the treatment of RA. The source of research support Canadian Institutes of Health Research