論文 - 詳細
| RRC ID | 59881 |
|---|---|
| 著者 | Endo K, Kito H, Tanaka R, Kajikuri J, Tanaka S, Elboray EE, Suzuki T, Ohya S. |
| タイトル | 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. |
| ジャーナル | Int J Mol Sci |
| Abstract |
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)-1α 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-1α 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-K2P5.1 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. |
| 巻・号 | 21(1) |
| 公開日 | 2019-12-19 |
| DOI | 10.3390/ijms21010038 |
| PII | ijms21010038 |
| PMID | 31861667 |
| PMC | PMC6981474 |
| MeSH | Animals Benzamides / pharmacology CD4-Positive T-Lymphocytes / metabolism* Cell Hypoxia Cell Line Dextran Sulfate / adverse effects Disease Models, Animal Gene Expression Regulation Humans Hypoxia-Inducible Factor 1, alpha Subunit / genetics* Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Inflammatory Bowel Diseases / chemically induced Inflammatory Bowel Diseases / genetics* Inflammatory Bowel Diseases / metabolism Mice Potassium Channels, Tandem Pore Domain / genetics* Potassium Channels, Tandem Pore Domain / metabolism Sirtuin 1 / genetics Sirtuin 1 / metabolism Thymocytes / cytology Thymocytes / metabolism |
| IF | 4.183 |
| 引用数 | 0 |
| 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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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CTLL-2(RCB0637) |