| RRC ID |
43670
|
| Author |
Takeshita H, Kitano M, Iwasaki T, Kitano S, Tsunemi S, Sato C, Sekiguchi M, Azuma N, Miyazawa K, Hla T, Sano H.
|
| Title |
Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-κB ligand (RANKL) expression in rheumatoid arthritis.
|
| Journal |
Biochem Biophys Res Commun
|
| Abstract |
Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-κB ligand (RANKL) in RA synoviocytes and CD4(+) T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4(+) T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4(+) T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-α in MH7A cells and CD4(+) T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4(+) T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.
|
| Volume |
419(2)
|
| Pages |
154-9
|
| Published |
2012-3-9
|
| DOI |
10.1016/j.bbrc.2012.01.103
|
| PII |
S0006-291X(12)00150-7
|
| PMID |
22326262
|
| PMC |
PMC3857967
|
| MeSH |
Arthritis, Rheumatoid / immunology*
CD4-Positive T-Lymphocytes / immunology
Cells, Cultured
GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
Humans
Lysophospholipids / metabolism*
RANK Ligand / biosynthesis*
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Receptors, Lysosphingolipid / metabolism*
Signal Transduction
Sphingosine / analogs & derivatives*
Sphingosine / metabolism
Synovial Fluid / immunology
|
| IF |
2.985
|
| Times Cited |
24
|
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
MH7A(RCB1512) |
