Studies on the Dynamics of Biogenic Amines in Inflammatory Reactions

生物胺在炎症反应中的动力学研究

• 批准号: 62570080
• 负责人: ENDO Yasuo
• 金额: $ 1.34万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570080/
• 关键词: Histamine; Serotonin; Histidine Decarboxylase; Ornithine Decarboxylase; Interleukin-1; Tumor Necrosis Factor; Inflammation; 血糖低下; 肝障害; インターロイキンー1; 腫瘍懐死因子; エンドトキシン

Histamine is formed by histidine decarboxylase (HDC). Ornithine decarboxylase (ODC) is a rate-limiting enzyme in polyamine synthesis. The author had clarified the followings before the term of this grant-in-aid: (1) The injections of some kinds of inflammatory agents into mice induce HDC and ODC activities reaching peaks within 3 to 5 h in the tissues such as liver, lung, spleen and bone marrow. In the liver, serotonin is also accumulated. (2) Macrophages may participate in the induction of these responses. (3) P388Dl cells, a macrophage cell line, produce the factors capable of inducing all these responses. The molecular weight and isoelectric points of the factors are identical with those of interleukin-1 (IL-1), an important immuno-regulator. (4) Pharmacological suties suggest that the accumulation of 5HT in the liver may become a cause producing hypoglycaemia and hepatitis.During the term of the grant-in-aid, the followings were clarified: (5) IL-1 and TNF (tumor necrosis factor), … More products of macrophages, stimulate or suppress the growth of some types of tumor cells. These effects correlate to the expression or suppression of ODC activity in the cells. (6) Recombinant human IL-1 and TNF also induce all the responses as the inflammatory agents did. In addition, the combination of IL-1 and TNF enhanced these responses. These results confirms the observations in (3) and indicate that IL-1 and/or TNF can be regulators of these responses. (7) The accumulation of 5ht in the liver is due to the modilization of 5HT from other sites. Platelets may be involved in this mechanism.Conclusion: The mechainisms of the dynamics of the biogenic amines described above intimately correlate to the regulation of inflammatory or immune responses. The present and fufure fruits of this project will provide new clues for understanding inflammation of immune responses.One of two papers concerning (6) is in press and the other is in preparation. Further experiments are necessary for the publication of (7). The research on (5) was collaborated with National Cancer Institute of USA (Frederick, MD). Less

组胺由组氨酸脱羧酶 (HDC) 形成。鸟氨酸脱羧酶（ODC）是多胺合成中的限速酶。作者在本次资助期限前明确了以下几点：（1）给小鼠注射某些炎症剂，可导致肝、肺、脾、骨髓等组织中的HDC和ODC活性在3～5小时内达到峰值。在肝脏中，血清素也会积累。 (2)巨噬细胞可能参与这些反应的诱导。 (3)P388D1细胞，一种巨噬细胞系，产生能够诱导所有这些反应的因子。该因子的分子量和等电点与重要的免疫调节剂白介素-1（IL-1）相同。 （4）药理学研究表明，5HT在肝脏中的蓄积可能成为引起低血糖和肝炎的原因。资助期间明确了以下内容：（5）IL-1和TNF（肿瘤坏死因子）等巨噬细胞的产物，刺激或抑制某些类型肿瘤细胞的生长。这些效应与细胞中 ODC 活性的表达或抑制相关。 (6)重组人IL-1和TNF也像炎症因子一样诱导所有反应。此外，IL-1 和 TNF 的组合增强了这些反应。这些结果证实了 (3) 中的观察结果，并表明 IL-1 和/或 TNF 可以调节这些反应。 (7)肝脏中5ht的积累是由于来自其他部位的5HT的修饰所致。血小板可能参与了这一机制。结论：上述生物胺的动力学机制与炎症或免疫反应的调节密切相关。该项目现在和未来的成果将为理解免疫反应的炎症提供新的线索。关于（6）的两篇论文之一正在印刷中，另一篇正在准备中。 (7) 的发表需要进一步的实验。 (5) 的研究是与美国国家癌症研究所（Frederick，MD）合作进行的。较少的

项目成果

遠藤 康男: British J. Pharmacol.90. 161-165 (1987)

Yasuo Endo：英国 J. Pharmacol.90（1987）。

Yasuo Endo: "Role of ornithine decarboxylase in the regulation of cell growth by interleukin-1 and tumor necrosis factor" J. Immunol.141. 2342-2348 (1988)

Yasuo Endo：“鸟氨酸脱羧酶在白介素-1 和肿瘤坏死因子调节细胞生长中的作用”J.Immunol.141。

Yasuo Endo.: British J.Pharmacol.90. 161-165 (1987)

Yasuo Endo.：英国 J.Pharmacol.90。

Yasuo Endo.: J.Immunol.141. 2342-2348 (1988)

Yasuo Endo.：J.Immunol.141。

Yasuo Endo: "Induction of histidine and ornithine decarboxylase activities in mouse tissues by recombinant interleukin-1 and tumor necrosis factor" Biochem. Pharmacol.(1989)

Yasuo Endo：“通过重组白细胞介素 1 和肿瘤坏死因子诱导小鼠组织中的组氨酸和鸟氨酸脱羧酶活性”Biochem。