RRC ID 43670
著者 Takeshita H, Kitano M, Iwasaki T, Kitano S, Tsunemi S, Sato C, Sekiguchi M, Azuma N, Miyazawa K, Hla T, Sano H.
タイトル Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-κB ligand (RANKL) expression in rheumatoid arthritis.
ジャーナル 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.
巻・号 419(2)
ページ 154-9
公開日 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
引用数 24
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MH7A(RCB1512)