| Title |
Activation of fibroblast-like synoviocytes derived from rheumatoid arthritis via lysophosphatidic acid-lysophosphatidic acid receptor 1 cascade
|
|---|---|
| Published in |
Arthritis Research & Therapy, October 2014
|
| DOI | 10.1186/s13075-014-0461-9 |
| Pubmed ID | |
| Authors |
Yoshishige Miyabe, Chie Miyabe, Yoshiko Iwai, Waka Yokoyama, Chiyoko Sekine, Kazutaka Sugimoto, Masayoshi Harigai, Masayuki Miyasaka, Nobuyuki Miyasaka, Toshihiro Nanki |
| Abstract |
IntroductionLysophosphatidic acid (LPA) is a bioactive lipid that binds to G protein-coupled receptors (LPA1¿6). Recently, we reported that abrogation of LPA receptor 1 (LPA1) ameliorated murine collagen-induced arthritis, probably via inhibition of inflammatory cell migration, Th17 differentiation and osteoclastogenesis. In this study, we examined the importance of the LPA-LPA1 axis in cell proliferation, cytokine / chemokine production, and lymphocyte transmigration in fibroblast-like synoviocytes (FLSs) obtained from the synovium of rheumatoid arthritis (RA).MethodsFLSs were prepared from synovial tissues of RA patients. Expression of LPA1¿6 was examined by quantitative real-time reverse transcription-polymerase chain reaction. Cell surface LPA1 expression was analyzed by flow cytometry. Cell proliferation was analyzed by cell counting kit. Production of interleukin (IL)-6, vascular endothelial growth factor (VEGF), CC chemokine ligand 2 (CCL2), metalloproteinase-3 (MMP-3) and CXC chemokine ligand 12 (CXCL12) was measured by enzyme-linked immunosorbent assay. Pseudoemperipolesis was evaluated using a coculture of RA FLSs and T or B cells. Cell motility was examined by the scrape motility assay. Expression of adhesion molecules was determined by flow cytometry.ResultsThe expression of LPA1 messenger ribonucleic acid (mRNA) and cell surface LPA1 expression was higher in RA FLSs than that in FLSs from osteoarthritis. Stimulation with LPA enhanced the proliferation of RA FLSs and the production of IL-6, VEGF, CCL2, and MMP-3 by FLSs, which were suppressed by an LPA1 inhibitor (LA-01). Ki16425, another LPA1 antagonist, also suppressed IL-6 production by LPA-stimulated RA FLSs. However, the production of CXCL12 was not altered by stimulation with LPA. LPA induced the pseudoemperipolesis of T and B cells cocultured with RA FLSs, which was suppressed by LPA1 inhibition. In addition, LPA enhanced the migration of RA FLSs and expression of vascular cell adhesion molecule and intercellular adhesion molecule on RA FLSs, which were also inhibited by an LPA1 antagonist.ConclusionsCollectively, these results indicate that LPA-LPA1 signaling contributes to the activation of RA FLSs. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 3% |
| Unknown | 33 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 24% |
| Student > Master | 8 | 24% |
| Student > Ph. D. Student | 3 | 9% |
| Student > Postgraduate | 3 | 9% |
| Student > Doctoral Student | 2 | 6% |
| Other | 3 | 9% |
| Unknown | 7 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 24% |
| Agricultural and Biological Sciences | 5 | 15% |
| Biochemistry, Genetics and Molecular Biology | 5 | 15% |
| Immunology and Microbiology | 3 | 9% |
| Chemistry | 2 | 6% |
| Other | 3 | 9% |
| Unknown | 8 | 24% |
Attention Score in Context
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#22,756,649
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Outputs from Arthritis Research & Therapy
#3,132
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Outputs of similar age from Arthritis Research & Therapy
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