Pathophysiological role of ET-1(1-31) on the inflammatory diseases.

ET-1(1-31)对炎症性疾病的病理生理作用。

• 批准号: 12557008
• 负责人: TAMAKI Toshiaki
• 金额: $ 6.59万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557008/
• 关键词: ET-1(1-31); Monocyte; Mesangium cell; MCP-1; Reactive oxygen species; Electron paramagnetic resonance; JNK; AP-1; Endothelin-1(1-31); mesangium cell; glomerulus; p38MAP kinase; antioxidants; chemotactic effect; monocyte; human mesangial cel

1) ET- 1(1-31) exhibited chemotactic activities toward human neutrophils and monocytes as an inflammatory mrdiator. The chemotactic effects induced by ET-1(1-31) was inhibited by BQ123, an ET_A receptor antagonist, but not by BQ788, an ET_B receptor antagonist.2) ET-1(1-31) directly cause the migration of mesangial cells and may be responsible for recruitment of mononuclear cells mediated through the mesangial cell activation. Since human cymase has been reported to be involved in glomerular disease, ET-1 (1-31) may be one of the mediators.3) ET-1(1-31) caused a significant increase in the electron paramagnetic resonance signal of the DMPO/OH radical spin adduct in rat aortic smooth muscle cells(RASMC). Antioxidants inhibit ET-1(1-31)-induced RASMC proliferation by inhibiting reactive oxygen species. The underlying mechanisms of the inhibition of cellular proliferation by antioxidants may be explained, in part, by the inhibition of JNK activation and the resultant inhibition of AP-1-DNA binding.4) Before surgery in patients with abdominal aortic aneurysma, plasma concentrations of ET-1(1-31) were higher than those in healthy individuals. After surgery, ET-1(1-31) in plasma decreased to the levels similar to those of healthy subjects.

1)ET- 1（1-31）对中性粒细胞和单核细胞具有趋化活性，是一种炎症调节剂。ET-1（1-31）诱导的趋化作用可被ET_A受体拮抗剂BQ 123抑制，而不被ET_B受体拮抗剂BQ 788抑制。2）ET-1（1-31）可直接引起系膜细胞迁移，并可能通过激活系膜细胞参与单核细胞的募集。3）ET-1（1 - 31）可使大鼠主动脉平滑肌细胞（RASMC）DMPO/OH自由基自旋加合物的电子顺磁共振信号显著增强。抗氧化剂通过抑制活性氧抑制ET-1（1-31）诱导的RASMC增殖。抗氧化剂抑制细胞增殖的潜在机制可能部分通过抑制JNK活化和由此产生的AP-1-DNA结合的抑制来解释。4）腹主动脉瘤患者手术前血浆ET-1（1-31）浓度高于健康个体。术后血浆ET-1（1-31）水平下降至与正常人相近。

项目成果

M.Yoshizumi: "Effect of endothelin-1(1-31) on the human mesangial cell proliferation"Jap.J.Pharmaclo.. 84. 146-155 (2000)

M.Yoshizumi：“内皮素-1(1-31)对人系膜细胞增殖的影响”Jap.J.Pharmaclo..84.146-155(2000)

Daisuke Inui: "Effect of endothelin-1(1-31) on p38 mitogen-activated protein kinase in cultured human mesangial cells"Life Sciences. 68・. 635-645 (2000)

Daisuke Inui：“内皮素-1（1-31）对培养的人肾小球膜细胞中p38丝裂原激活蛋白激酶的影响”生命科学68·635-645（2000）。

吉栖正典: "エンドセリン-1(1-31)の腎作用"腎と透析. 49・4. 739-743 (2000)

Masanori Yoshisu：“内皮素-1（1-31）的肾效应”肾脏和透析49・4（2000）。

P.Cui: "A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes"J.Leukocyte Biology. 70. 306-312 (2001)

P.Cui：“一种新型的具有生物活性的 31 个氨基酸内皮素-1 是一种针对人类中性粒细胞和单核细胞的有效趋化肽”J.白细胞生物学。

Y. Suzaki, M. Yoshizumi, Y. Yamashita, S. Abe, K. Tsuchiya, Y. Satoh, Y. Kuroda, K. Horike, M. Kano, Y. Fukuta, T. Kitaichi, T. Hori, Y. Masuda, T. Kitagawa, K. Minakuchi, and T. Tamaki: "Determination of plasma concentrations of endothelin-1(1-31) and en

Y. Suzaki、M. Yoshizumi、Y. Yamashita、S. Abe、K. Tsuchiya、Y. Satoh、Y. Kuroda、K. Horike、M. Kano、Y. Fukuta、T. Kitaichi、T. Hori、Y.