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マスト細胞の分化とアラキドン酸代謝酵素群の発現調節

肥大细胞分化和花生四烯酸代谢酶表达的调节

基本信息

批准号：
12139206
负责人：
村上誠
金额：
$ 26.43万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2003
项目状态：
已结题

项目摘要

本年度は、申請者が昨年度までに同定、解析を進めてきたマスト細胞分化随伴誘導遺伝子NDRG1とMMIG-1について、以下の結果を得た。NDRG-1:NDRG1欠損マウスより骨髄由来培養マスト細胞(BMMC)を調整し、その表現型を対照マウス由来のBMMCと比較検討した。その結果、BMMCの形態や細胞増殖、分泌顆粒から見た成熟度はNDRG1欠損の影響を受けず、FcεRl架橋に伴う細胞内Ca^<2+>流入や脱顆粒反応も変化がなかった。一方、本細胞を線維芽細胞との共培養により結合組織型マスト細胞(CTMC)様に分化成熟されると、FcεRl架橋あるいはcompound 48/80刺激依存的な脱顆粒応答がNDRG1欠損マウスにおいて有意に減少し、従来NDRG1の過剰発現に伴い脱顆粒の亢進を認めた実験結果と合致する結果が得られた。そこで対照およびNDRG1欠損マウス由来BMMCの間で発現が変動する遺伝子群について、DNA chipを用いた一括同定を実施した結果、特にCTMC様に分化させた細胞群において、細胞骨格系に関与する遺伝子群の著明な発現変動を認めた。現在、NDRG1欠損がマウス個体のアレルギー応答に及ぼす影響を検討中である。MMIG-1:免疫組織化学染色により、MMIG-1がアトピー性皮膚炎発症マウスの局所マスト細胞に分布することがわかった。アデノウイルスを用いてMMIG-1をBMMCに過剰発現させ、その機能を解析した結果、MMIG-1の発現はマスト細胞の分化成熟、脱顆粒応答には影響を与えなかったが、遅発的PGD_2産生が有意に抑制され、更に老化したBMMCに対してはアポトーシスを誘導した。以上のことから、MMIG-1はマスト細胞の長期的活性化を抑制し、更に不要となったマスト細胞にアポトーシスを誘導することによって、炎症応答を終結させる方向に機能する分子であることが予想された。現在、MMIG-1 siRNAを用いて本仮説の検証を進めている。

The current year and the applicant last year agreed and analyzed that the cell differentiation was accompanied by NDRG1MMIG-1 cell differentiation, and the following results were obtained. The cause of NDRG-1:NDRG1 is that the cells (BMMC) are divided into two types: the number of cells (BMMC), the size of the cell (s), the shape of the cell (s), the shape of the image (s), the cause of the disease (BMMC) and the size of the cell (s). The results showed that the morphology of BMMC, the proliferation of cells, the secretion of grains, the maturity of NDRG1, the deficiency of NDRG1, the scaffolding of Fc ε Rl and the influx of intracellular Ca ^ & lt;2+> into threshing and retrograining. On the one hand, the cell line maintenance germ cell co-culture was combined with tissue-type cell culture (CTMC) to differentiate into mature cells, and Fc ε Rl frame to induce compound 480.These exfoliated cells were dependent on stimulation. The response was that NDRG1 failed to induce intentional depletion, and the results of NDRG1 screening were associated with increased degranulation activity. The reason why the NDRG1 is not valid is that the subgroup of the mobile phone is detected, the subgroup of the DNA chip is identified, the results of the experiment, the differentiation of the cell population, the cell population of the bone cell and the subgroup of the cell are identified. The results show that the subgroup of the cell, the subgroup of the cell and the subgroup of the cell. At present, NDRG1 is short of information about how to answer and how much information you need to know. MMIG-1: immunohisto-chemical staining was used to detect dermatitis, and the distribution of cells in patients with dermatitis caused by MMIG-1 was significantly higher than that in normal controls. The results of MMIG-1 BMMC analysis, the results of MMIG-1 analysis, the differentiation and maturation of the cells, the effects of degranulation, the intentional inhibition and aging of the PGD_2 were used to analyze the results, the results of the analysis of the results, the differentiation and maturation of the cells, degranulation and aging. The abovementioned disease, MMIG-1 infection, long-term activation of the cell, not to mention the activation of the cell, the activation of the cell for a long time. At present, MMIG-1 siRNA is currently in the process of entering the market.