論文 - 詳細
| RRC ID | 42827 |
|---|---|
| 著者 | Maeda T, Hirayama M, Kobayashi D, Miyazawa K, Tamai I. |
| タイトル | Mechanism of the regulation of organic cation/carnitine transporter 1 (SLC22A4) by rheumatoid arthritis-associated transcriptional factor RUNX1 and inflammatory cytokines. |
| ジャーナル | Drug Metab Dispos |
| Abstract |
Recently, it was reported that the organic cation/carnitine transporter 1 (OCTN1, SLC22A4) is associated with chronic inflammatory diseases, such as rheumatoid arthritis (RA) and Crohn's disease. OCTN1 in humans is expressed in synovial tissues of individuals with rheumatoid arthritis. Furthermore octn1 in mice is expressed in inflamed joints with collagen-induced arthritis, a model of human arthritis, but not in the joints of normal mice. OCTN1 should be involved in the inflammatory disease and in the present study, the regulatory mechanism of OCTN1 expression was characterized using the human fibroblast-like synoviocyte cell line MH7A, derived from RA patients. A luciferase-reporter gene assay and gel shift assay demonstrated that RUNX1, which is an essential hematopoietic transcription factor associated with acute myeloid leukemia and is related to RA and Sp1, is involved in the regulation of OCTN1 promoter activity. Inflammatory cytokines such as interleukin-1beta and tumor necrosis factor-alpha increased the expression of OCTN1 mRNA. Furthermore, overexpression of nuclear factor-kappaB (NF-kappaB) activated promoter activity of OCTN1. These results clearly demonstrate that expression of OCTN1 is regulated by various factors, including RUNX1, inflammatory cytokines, and NF-kappaB, all of which are also related to the pathogenesis of RA. Further studies on the physiological substrate(s) of OCTN1 should be done to clarify the roles of OCTN1 in these diseases. |
| 巻・号 | 35(3) |
| ページ | 394-401 |
| 公開日 | 2007-3-1 |
| DOI | 10.1124/dmd.106.012112 |
| PII | dmd.106.012112 |
| PMID | 17142562 |
| MeSH | Arthritis, Rheumatoid / metabolism* Binding Sites Cell Line Core Binding Factor Alpha 2 Subunit / genetics Core Binding Factor Alpha 2 Subunit / metabolism* Humans Interleukin-1beta / pharmacology Mutation NF-kappa B / genetics NF-kappa B / metabolism* Organic Cation Transport Proteins / genetics* Promoter Regions, Genetic RNA, Messenger / metabolism Sp1 Transcription Factor / genetics Sp1 Transcription Factor / metabolism* Symporters Tumor Necrosis Factor-alpha / pharmacology |
| IF | 3.231 |
| 引用数 | 29 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 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 | MH7A(RCB1512) |