{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:58:36Z","timestamp":1789167516503,"version":"build-2803163510"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,11,16]],"date-time":"2017-11-16T00:00:00Z","timestamp":1510790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology and Japan Society for the promotion of Science","doi-asserted-by":"publisher","award":["15K09518"],"award-info":[{"award-number":["15K09518"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Tumour necrosis factor alpha (TNF)-\u03b1-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-\u03b1 was increased significantly through lipopolysaccharide (LPS) stimulation. Immunoblot analysis revealed that phosphorylated (p-)nuclear factor kappa B (NF-\u03baB) was increased after LPS stimulation and degradation of nuclear factor kappa B inhibitor alpha (I\u03baB\u03b1) 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-\u03b1 and IL-6 through NF-\u03baB and STAT-3 pathways, resulting in the generation of RA.<\/jats:p>","DOI":"10.1111\/cei.13076","type":"journal-article","created":{"date-parts":[[2017,10,28]],"date-time":"2017-10-28T09:16:38Z","timestamp":1509182198000},"page":"338-348","source":"Crossref","is-referenced-by-count":8,"title":["Clinical and functional significance of STEAP4-splice variant in CD14+ monocytes in patients with rheumatoid arthritis"],"prefix":"10.1093","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0878-4017","authenticated-orcid":false,"given":"H","family":"Ebe","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Kurata","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Tsuboi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Sumida","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,16]]},"reference":[{"key":"2021120808192594900_cei13076-bib-0001","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nri2094","article-title":"Cytokines in the pathogenesis of rheumatoid 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