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抗P抗体はSLEにおいて血中・脳中トリプトファンの低下を介して気分障害を引き起こす
http://hdl.handle.net/10191/0002000467
http://hdl.handle.net/10191/00020004676d0a7ca6-e7e4-4c8f-adec-b52c826f2b59
| 名前 / ファイル | ライセンス | アクション |
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本文 (2.29MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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| 公開日 | 2022-05-10 | |||||||||
| タイトル | ||||||||||
| タイトル | Mood Disorder in Systemic Lupus Erythematosus Induced by Antiribosomal P Protein Antibodies Associated with Decreased Serum and Brain Tryptophan | |||||||||
| 言語 | en | |||||||||
| タイトル | ||||||||||
| タイトル | 抗P抗体はSLEにおいて血中・脳中トリプトファンの低下を介して気分障害を引き起こす | |||||||||
| 言語 | ja | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| 資源タイプ | ||||||||||
| 資源 | http://purl.org/coar/resource_type/c_db06 | |||||||||
| タイプ | doctoral thesis | |||||||||
| アクセス権 | ||||||||||
| アクセス権 | open access | |||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
| 著者 |
張, 高正
× 張, 高正
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| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Antiribosomal P protein (anti-P) autoantibodies commonly develop in patients with systemic lupus erythematosus. We have previously established hybridoma clones producing anti-P mAbs. In this study, we explored the pathogenesis of behavioral disorders induced by anti-P Abs using these mAbs. New Zealand Black x New Zealand White F1, New Zealand White, C57BL/6, and BALB/c mice were treated with 1 mg of anti-P Abs once every 2 wk. The behavioral disorder was evaluated by the tail suspension test, forced swim test, and open field test. Following administration of anti-P Abs, New Zealand Black x New Zealand White F1 and C57BL/6 mice developed depressive behavior and showed increased anxiety with elevated serum TNF-α and IL-6 levels. Anti-P Abs were not deposited in the affected brain tissue; instead, this mood disorder was associated with lower serum and brain tryptophan concentrations. Tryptophan supplementation recovered serum tryptophan levels and prevented the behavioral disorder. TNF-α and IL-6 were essential for the decreased serum tryptophan and disease development, which were ameliorated by treatment with anti–TNF-α neutralizing Abs or dexamethasone. Peritoneal macrophages from C57BL/6 mice produced TNF-α, IL-6, and IDO-1 via interaction with anti-P Abs through activating FcγRs, which were required for disease development. IVIg, which has an immunosuppressive effect partly through the regulation of FcγR expression, also prevented the decrease in serum tryptophan and disease development. Furthermore, serum tryptophan concentrations were decreased in the sera of systemic lupus erythematosus patients with anti-P Abs, and lower tryptophan levels correlated with disease activity. Our study revealed some of the molecular mechanisms of mood disorder induced by anti-P Abs. | |||||||||
| 言語 | en | |||||||||
| 内容記述 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | Journal of immunology. 2021, 206(8), 1729-1739. | |||||||||
| 言語 | en | |||||||||
| DOI | ||||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | https://doi.org/10.4049/jimmunol.2000260 | |||||||||
| 権利 | ||||||||||
| 言語 | en | |||||||||
| 権利情報 | 【○!C】 2021 by TheAmericanAssociation of Immunologists, Inc. | |||||||||
| 学位名 | ||||||||||
| 言語 | ja | |||||||||
| 学位名 | 博士（医学） | |||||||||
| 学位授与機関 | ||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||
| 学位授与機関識別子 | 13101 | |||||||||
| 言語 | ja | |||||||||
| 学位授与機関名 | 新潟大学 | |||||||||
| 言語 | en | |||||||||
| 学位授与機関名 | Niigata University | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2021-09-21 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第4935号 | |||||||||
| 学位記番号 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | 新大院博(医)第1025号 | |||||||||
| 言語 | ja | |||||||||
