{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:48:22Z","timestamp":1790430502953,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,9,9]],"date-time":"2014-09-09T00:00:00Z","timestamp":1410220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Scientific Research from the Japan Society for the Promotion of Science","award":["12470471"],"award-info":[{"award-number":["12470471"]}]},{"name":"Scientific Research from the Japan Society for the Promotion of Science","award":["14571982"],"award-info":[{"award-number":["14571982"]}]},{"name":"Scientific Research from the Japan Society for the Promotion of Science","award":["17791555"],"award-info":[{"award-number":["17791555"]}]},{"name":"Scientific Research from the Japan Society for the Promotion of Science","award":["24792332"],"award-info":[{"award-number":["24792332"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2015,8]]},"abstract":"Background and Objective<\/jats:title>Tumor necrosis factor alpha (TNF<\/jats:styled-content>\u2010\u03b1) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF<\/jats:styled-content>\u2010\u03b1 gene regulation is not well elucidated. We previously identified a novel region located from \u2212550 to \u2212487 in human TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> promoter that did not contain the reported binding sites for nuclear factor kappa B<\/jats:styled-content> (NF<\/jats:styled-content>\u2010\u03baB) but showed lipopolysaccharide (LPS<\/jats:styled-content>)\u2010induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> expression.<\/jats:p><\/jats:sec>Material and Methods<\/jats:title>To identify DNA<\/jats:styled-content>\u2010binding proteins that bound to the target region of TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> promoter, a cDNA<\/jats:styled-content> library from LPS<\/jats:styled-content>\u2010stimulated human monocytic cell line THP<\/jats:styled-content>\u20101 was screened using a yeast one\u2010hybrid system. Cellular localizations of the DNA<\/jats:styled-content>\u2010binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS<\/jats:styled-content>\u2010stimulated THP<\/jats:styled-content>\u20101 cells were identified by western blot analysis. Expression of mRNA<\/jats:styled-content> of the protein in the cells was quantified by real\u2010time polymerase chain reaction<\/jats:styled-content>. Electrophoretic mobility shift assays were performed to confirm the DNA<\/jats:styled-content>\u2010binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> expression.<\/jats:p><\/jats:sec>Results<\/jats:title>Several candidates were identified from the cDNA<\/jats:styled-content> library and transactivation\u2010responsive DNA<\/jats:styled-content>\u2010binding protein 43 (TARDBP<\/jats:styled-content>43; TDP<\/jats:styled-content>\u201043) was focused on. Western blot analysis revealed that nuclear TDP<\/jats:styled-content>\u201043 protein was increased in the LPS<\/jats:styled-content>\u2010stimulated THP<\/jats:styled-content>\u20101 cells. Expression of TDP<\/jats:styled-content>\u201043<\/jats:italic> mRNA<\/jats:styled-content> was already enhanced before TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> induction by LPS<\/jats:styled-content>. Electrophoretic mobility shift assay<\/jats:styled-content> analysis showed that nuclear extracts obtained by overexpressing FLAG<\/jats:styled-content>\u2010tagged TDP<\/jats:styled-content>\u201043 bound to the \u2212550 to \u2212487 TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> promoter fragments. Overexpression of TDP<\/jats:styled-content>\u201043 in THP<\/jats:styled-content>\u20101 cells resulted in an increase of TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> expression. Knockdown of TDP<\/jats:styled-content>\u201043 in THP<\/jats:styled-content>\u20101 cells downregulated TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> expression.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>We identified TDP<\/jats:styled-content>\u201043 as one of the novel TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> factors and found that it bound to the LPS<\/jats:styled-content>\u2010responsive element in the TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> promoter to increase TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic> expression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12227","type":"journal-article","created":{"date-parts":[[2014,9,9]],"date-time":"2014-09-09T12:34:01Z","timestamp":1410266041000},"page":"452-460","source":"Crossref","is-referenced-by-count":15,"title":["Identification of transactivation\u2010responsive DNA<\/scp>\u2010binding protein 43 (TARDBP<\/scp>43; TDP<\/scp>\u201043) as a novel factor for TNF<\/scp>\u2010\u03b1<\/i> expression upon lipopolysaccharide stimulation in human monocytes"],"prefix":"10.1111","volume":"50","author":[{"given":"H.","family":"Murata","sequence":"first","affiliation":[{"name":"Department of Periodontology and Endodontology Institute of Health Biosciences The University of Tokushima Graduate School Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Hattori","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Dentistry Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology\u2010Periodontal Science Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama 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