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Studies on Enhancement of Phagocytosis and Cytotoxicity in Macrophages by IL-18-Stimulation.
http://hdl.handle.net/10191/27260
316316b5-4795-4432-afac-5d263781c1ce
名前 / ファイル | ライセンス | アクション | |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2014-05-19 | |||||
タイトル | ||||||
タイトル | Studies on Enhancement of Phagocytosis and Cytotoxicity in Macrophages by IL-18-Stimulation. | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Studies on Enhancement of Phagocytosis and Cytotoxicity in Macrophages by IL-18-Stimulation. | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_46ec | |||||
タイプ | thesis | |||||
その他のタイトル | ||||||
その他のタイトル | インターロイキン18刺激によるマクロファージの貪食機能および細胞傷害性活性増強に関する研究 | |||||
著者 |
Xu, Henan
× Xu, Henan |
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著者別名 | ||||||
識別子 | ||||||
識別子 | 50384 | |||||
識別子Scheme | WEKO | |||||
姓名 | ||||||
姓名 | 徐, 賀楠 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Inoculation of mice with the murine NFSA cell line caused the formation of large tumors with necrotic tumor cores. FACS analysis revealed accumulations of CD11b+ cells in the tumors. Microarray analysis indicated that the NFSA cells expressed a high level of the pro-inflammatory factor interleukin-18 (il-18), which is known to play a critical role in macrophages. However, little is known about the physiological function of IL-18-stimulated macrophages. Here, we provide direct evidence that IL-18 enhances the phagocytosis of RAW264 cells and peritoneal macrophages, accompanied by the increased expression of tumor necrosis factor (tnf-α), interleukin-6 (il-6) and inducible nitric oxide synthase (Nos2). IL-18-stimulated RAW264 cells showed an enhanced cytotoxicity to endothelial F-2 cells via direct cell-to-cell interaction and the secretion of soluble mediators, including NOS2 derived NO. Taken together, these results demonstrate that tumor-derived IL-18 plays an important role in the phagocytosis of macrophages and that IL-18-stimulated macrophages may damage tumor endothelial cells. | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | マウス培養細胞株,NFSA細胞をマウス皮下に移植すると巨大な腫瘍を形成し,その中心部は壊死を起こす。FACS (自動細胞解析捕集装置) を用いてこのNFSA腫瘍中の細胞を解析すると,マクロファージなどに発現の認められるCD11b陽性細胞の蓄積があることが判った。NFSA細胞で発現している遺伝子をDNAマイクロアレイ解析により解析すると,マクロファージで重要な役割を担うことが知られている炎症性インターロイキン-18(IL-18)を高発現していた。以上の結果から,IL-18とマクロファージの関係が予想されたが,これまでにIL-18により活性化されたマクロファージがどのような生理活性を担うかについては詳細に解明されていない。 本論文ではIL-18がマクロファージ細胞株であるRAW264細胞およびFACSにより単離したマウス腹腔由来マクロファージの貪食作用を強化することを,これらの細胞への蛍光マイクロビーズの取り込みを測定することにより明らかにした。このとき,このIL-18により活性化されたマクロファージでは腫瘍壊死因子(TNF-α),インターロイキン-6(IL-6)および誘導可能な一酸化窒素合成酵素(Nos2)等の遺伝子発現も増加することを明らかにするとともに,抗IL-18中和抗体を用いた実験から,これらがIL-18の作用によるものであることを明確に示した。さらに,IL-18で刺激されたRAW264細胞を血管内皮細胞株F-2と共培養すると,細胞間相互作用によりF-2細胞はマクロファージにより傷害される事を明らかにした。また,共培養時にRAW264細胞とF-2細胞の直接接触を妨げた場合も,RAW264細胞はF-2細胞に対する傷害性を示したことから,マクロファージにより産生される何らかの可溶性物質もこの傷害に関与しているものと考えられた。これらを総合すると,IL-18刺激によりマクロファージの貪食能は増強されるとともに,血管内皮細胞に対して液性因子や細胞間相互作用を介して傷害を及ぼすことが明らかとなった。従って,高いIL-18産生能を示すNFSA腫瘍においては,このIL-18により腫瘍中のマクロファージが活性化されその細胞障害性活性が上昇して血管内皮細胞が傷害を受けることにより血管新生が阻害され,その結果,腫瘍細胞の壊死が誘導されると予想される。 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 学位の種類: 博士(理学). 報告番号: 甲第3917号. 学位記番号: 新大院博(理)甲第386号. 学位授与年月日: 平成26年3月24日 | |||||
書誌情報 | p. 1-61, 発行日 2014-03-24 | |||||
出版者 | ||||||
出版者 | 新潟大学 | |||||
著者版フラグ | ||||||
値 | ETD | |||||
学位名 | ||||||
学位名 | 博士(理学) | |||||
学位授与機関 | ||||||
学位授与機関名 | ||||||
学位授与機関名 | 新潟大学 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2014-03-24 | |||||
学位授与番号 | ||||||
学位授与番号 | 13101甲第3917号 | |||||
学位記番号 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 新大院博(理)甲第386号 |