{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:33:04Z","timestamp":1780320784642,"version":"3.54.1"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previous studies have reported the up-regulation of the two-pore domain K+ channel K2P5.1 in the CD4+ T cells of patients with multiple sclerosis (MS) and rheumatoid arthritis (RA), as well as in a mouse model of inflammatory bowel disease (IBD). However, the mechanisms underlying this up-regulation remain unclear. Inflammation-associated hypoxia is involved in the pathogenesis of autoimmune diseases, such as IBD, MS, and RA, and T cells are exposed to a hypoxic environment during their recruitment from inflamed tissues to secondary lymphoid tissues. We herein investigated whether inflammation-associated hypoxia is attributable to the increased expression and activity of K2P5.1 in the splenic CD4+ T cells of chemically-induced IBD model mice. Significant increases in hypoxia-inducible factor (HIF)-1\u03b1 transcripts and proteins were found in the splenic CD4+ T cells of the IBD model. In the activated splenic CD4+ T cells, hypoxia (1.5% O2) increased K2P5.1 expression and activity, whereas a treatment with the HIF inhibitor FM19G11 but not the selective HIF-2 inhibitor exerted the opposite effect. Hypoxia-exposed K2P5.1 up-regulation was also detected in stimulated thymocytes and the mouse T-cell line. The class III histone deacetylase sirtuin-1 (SIRT1) is a downstream molecule of HIF-1\u03b1 signaling. We examined the effects of the SIRT1 inhibitor NCO-01 on K2P5.1 transcription in activated CD4+ T cells, and we found no significant effects on the K2P5.1 transcription. No acute compensatory responses of K2P3.1\u2013K2P5.1 up-regulation were found in the CD4+ T cells of the IBD model and the hypoxia-exposed T cells. Collectively, these results suggest a mechanism for K2P5.1 up-regulation via HIF-1 in the CD4+ T cells of the IBD model.<\/jats:p>","DOI":"10.3390\/ijms21010038","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T09:50:33Z","timestamp":1576835433000},"page":"38","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Possible Contribution of Inflammation-Associated Hypoxia to Increased K2P5.1 K+ Channel Expression in CD4+ T Cells of the Mouse Model for Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Kyoko","family":"Endo","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan"},{"name":"Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Kito","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0598-0733","authenticated-orcid":false,"given":"Junko","family":"Kajikuri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3468-7694","authenticated-orcid":false,"given":"Satoshi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elghareeb E.","family":"Elboray","sequence":"additional","affiliation":[{"name":"Department of Complex Molecular Chemistry, The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan"},{"name":"Faculty of Science, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Complex Molecular Chemistry, The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-0667","authenticated-orcid":false,"given":"Susumu","family":"Ohya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1111\/j.1750-3639.2010.00407.x","article-title":"From the background to the spotlight: TASK channels in pathological conditions","volume":"20","author":"Bittner","year":"2010","journal-title":"Brain Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1113\/jphysiol.2014.287268","article-title":"The family of K2P channels: Salient structural and functional properties","volume":"593","author":"Feliciangeli","year":"2015","journal-title":"J. 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