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ケモカインならびにそのレセプターの病態生理学的役割の解析を通した抗炎症剤の開発
https://doi.org/10.24517/00050574
https://doi.org/10.24517/00050574ee9837e8-21db-4311-96df-ab93f69a5927
名前 / ファイル | ライセンス | アクション |
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CA-PR-MUKAIDA-N-kaken 2000-10p.pdf (628.6 kB)
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Item type | 報告書 / Research Paper(1) | |||||
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公開日 | 2018-04-20 | |||||
タイトル | ||||||
タイトル | ケモカインならびにそのレセプターの病態生理学的役割の解析を通した抗炎症剤の開発 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Pathophyiological and immunopharmacological studies on chemokines and their receptors | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_18ws | |||||
資源タイプ | research report | |||||
ID登録 | ||||||
ID登録 | 10.24517/00050574 | |||||
ID登録タイプ | JaLC | |||||
著者 |
向田, 直史
× 向田, 直史 |
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著者別表示 |
Mukaida, Naofumi
× Mukaida, Naofumi |
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書誌情報 |
平成11(1999)年度 科学研究費補助金 基盤研究(A) 研究成果報告書 en : 1999 Fiscal Year Final Research Report 巻 1998-1999, p. 10p., 発行日 2000-03 |
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出版者 | ||||||
出版者 | 金沢大学がん進展制御研究所 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 本研究を通して、以下の研究成果を挙げた。 1)マウス・メスの排卵直後に膣局所で産生されるインターロイキン8(IL-8)ホモログが、性周期依存的に起きる好中球の膣粘膜への浸潤を制御していることを明らかにした。 2)モノクロタリン投与による実験的肺高血圧モデルで、肺局所で産生される単球走化因子(MCP-1)が、肺へのマクロファージ浸潤とそれに引き続く肺の組織障害を制御している事を明らかにした。 3)IgA腎症で、急性型では尿中IL-8が上昇するのに対して、腎不全に移行しやすい慢性型では尿中MCP-1濃度の上昇がIL-8に比べて顕著であるなど、病型によって腎局所でケモカインが選択的に産生される可能性を認めた。 3)半月板形成性腎炎では、腎臓内で産生されるmacrophage inflammatory protein-1α(MIP-1α)が半月板形成に関与するのに対して、MCP-1が間質病変の成立に関与していることを示唆する結果を得た。 4)IL-8遺伝子を導入した癌細胞株を接種すると、接種部位での血管新生とともに腫瘍形成が亢進する事から、IL-8の血管新生作用を確認した。腫瘍の壊死部の近傍でIL-8蛋白・mRNAの発現が認められた。壊死部の近傍は低酸素状態であると考えられるので、種々のがん細胞株を低酸素状態に暴露したところ、IL-8遺伝子の転写ならびに産生が誘導された。さらに胃癌組織中の癌細胞そのものが、IL-8レセプターを発現していることも明らかになった。 5)活性化補体第5成分(C5a)刺激によって、単球細胞株でNF-κBならびにAP-1が活性化されることによって、IL-8遺伝子転写ならびに蛋白産生が誘導されることが明らかになった。 6)急性肝障害モデルで、インターフェロンγの組織障害への関与を明らかにした。 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | This study was performed to clarify the pathophysiological roles of chemokines and their receptors in various types of diseases. Through these studies, we obtained the results as follows. 1) Macrophage inflammatory protein (MIP)-2, a functional homologue of human interleukin-8 (IL-8), was produced periodically at mouse vaginal epithelium immediately after the ovulation. Moreover, locally produced MIP-2 was involved in postovulatory neutrophil migration into vagina. 2) Subcutaneous injection of monocrotaline into rats caused chronic pulmonary hypertension accompanied with intrapulmonary macrophage infiltration. Monocyte chemoattractant protein (MCP)-1 was produced at the onset of macrophage infiltration. The administration of anti-MCP-1 antibodies reduced macrophage infiltration and alleviated pulmonary hypertension. These results suggest that MCP-1 was involved in the pathogenesis of monocrotaline-induced pulmonary hypertension, through inducing macrophage infiltration. 3) In an acute typ e of IgA nephropathy, urinary IL-8 levels were increased with no increase in urinary MCP-1 levels. In contrast, in a chronic type of IgA nephropathy which is prone to develop chronic renal failure, urinary MCP-1 levels were markedly increased while urinary IL-8 levels were not. Moreover, we found that urinary MIP-lα and MCP-1 levels correlated with crescent formation and interstitial lesions in chronic crescentic glomerulonephritis, respectively. Thus, various chemokines were produced locally and differentially at the diseased kidney, thereby contributing to the establishment of various renal lesions. 4) Angiogenesis and tumor formation was enhanced by IL-8 cDNA transfection into gastric cancer cell lines. Moreover, we observed IL-8 mRNA and protein expression near necrotic areas in the tumor sites. Because the area close to necrosis is presumed to be hypoxic, we rendered human ovarian cancer and melanoma cell lines hypoxia. Hypoxia activated two types of transcription factors, AP-1 and NF-κBB, thereby inducing IL-8 production. Furthermore, we obtained definitive evidence on the presence of IL-8 receptors on human gastric cancer cells. Collectively, these results suggest that IL-8 may be involved in tumor progression by inducing angiogenesis and changing the phenotypes of cancer cells. 5) We observed that C5a activated AP-1 and NF-κB, thereby inducing IL-8 production in a human monocyte cell line. 6) We obtained the evidence that interferon-γ was involved in granuloma formation in Propinibacterium acnes-primed mice and subsequent lipopolysaccharide-induced liver tissue damage, by regulating macrophage infiltration and the production of several cytokines including tumor necrosis factor (TNF)-α IL-12, and IL-18. |
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内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 研究課題/領域番号:10044254, 研究期間(年度):1998-1999 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 出典:「ケモカインならびにそのレセプターの病態生理学的役割の解析を通した抗炎症剤の開発」研究成果報告書 課題番号10044254 (KAKEN:科学研究費助成事業データベース(国立情報学研究所)) 本文データは著者版報告書より作成 |
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著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/search/?qm=30182067 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10044254/ | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-10044254/100442541999kenkyu_seika_hokoku_gaiyo/ |