論文 - 詳細
| RRC ID | 56631 |
|---|---|
| 著者 | Ebe H, Matsumoto I, Kawaguchi H, Kurata I, Tanaka Y, Inoue A, Kondo Y, Tsuboi H, Sumida T. |
| タイトル | Clinical and functional significance of STEAP4-splice variant in CD14+ monocytes in patients with rheumatoid arthritis. |
| ジャーナル | Clin Exp Immunol |
| Abstract |
Tumour necrosis factor alpha (TNF)-α-induced adipose-related protein (TIARP) is a negative regulator of inflammation in arthritis model mice. In humans, six-transmembrane epithelial antigen of prostate 4 (STEAP4) (human counterpart of TIARP) is also expressed in CD14+ monocytes from patients with rheumatoid arthritis (RA). Recently, highly levels of exon 3-spliced variant STEAP4 (v-STEAP4) expression have been observed in porcine lung. The aim of this study is to elucidate the expression and functional role of v-STEAP4, comparing it with that of STEAP4, in the pathogenesis of arthritis. We identified v-STEAP4 in CD14+ cells. The expression of STEAP4 and v-STEAP4 was higher in patients with RA than in healthy participants. We also found that STEAP4 and v-STEAP4 were correlated positively with C-reactive protein and that their expression was decreased after treatment with an interleukin (IL)-6 antagonist in patients with RA. To investigate further the role of STEAP4 and v-STEAP4, we produced STEAP4 and v-STEAP4 over-expressing human monocytic cell lines (THP-1) for functional analysis. In the v-STEAP4 over-expressing cells, the production of IL-6 was suppressed significantly, but TNF-α was increased significantly through lipopolysaccharide (LPS) stimulation. Immunoblot analysis revealed that phosphorylated (p-)nuclear factor kappa B (NF-κB) was increased after LPS stimulation and degradation of nuclear factor kappa B inhibitor alpha (IκBα) was sustained, whereas p-signal transducer and activator of transcription 3 (STAT-3) was decreased with v-STEAP4. We identified specific up-regulation of v-STEAP4 in RA monocytes. V-STEAP4 might play a crucial role in the production of TNF-α and IL-6 through NF-κB and STAT-3 pathways, resulting in the generation of RA. |
| 巻・号 | 191(3) |
| ページ | 338-348 |
| 公開日 | 2018-3-1 |
| DOI | 10.1111/cei.13076 |
| PMID | 29080328 |
| PMC | PMC5801491 |
| MeSH | Animals Arthritis, Experimental / immunology Arthritis, Experimental / metabolism* Arthritis, Rheumatoid / immunology Arthritis, Rheumatoid / metabolism* Humans Interleukin-6 / metabolism Lipopolysaccharide Receptors / metabolism Lipopolysaccharides / immunology Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Monocytes / immunology* NF-kappa B / metabolism Oxidoreductases / genetics Oxidoreductases / metabolism* RNA Isoforms / genetics RNA Isoforms / metabolism* RNA Splicing STAT3 Transcription Factor / metabolism Signal Transduction Swine THP-1 Cells Tumor Necrosis Factor-alpha |
| IF | 3.711 |
| 引用数 | 4 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |