| 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
|
| リソース情報 |
| ヒト・動物細胞 |
THP-1(RCB1189) |
