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Comparison of anti-inflammatory activities between recombinant human lipocortin and glucocorticoid.

重组人脂皮质素与糖皮质激素抗炎活性的比较。

基本信息

批准号：
62870092
负责人：
OHUCHI Kazuo
金额：
$ 1.92万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

Lipocortin is reported as an anti-inflammatory protein which mediates anti-inflammatory actions of glucocorticoids. In this investigation, using human lipocortin synthesized biotechnologically by Biogen Research Co. (lipocortin-Biogen) or by Toray Industries Inc. (Lipocortin-Toray), we aimed to determine whether anti-inflammatory activities of lipocortin are comparable to those of glucocorticoids.(1) Lipocortin-Biogen inhibited TPA-induced release of radioactivity from [^3H] arachidonic acid-labeled macrophages in a dosedependent manner, but the effect was much weaker than that of dexamethasone.(2) In kaoline-induced air pouch type inflammation model, lipocortin-Biogen failed to inhibit vascular permeability increase during the period of 0 - 20 min, although PGE_2 level in the pouch fluid 20 min after the injection of kaolin was decreased dose-dependently.(3) In zymosan-induced air pouch type inflammation model, lipocortin-Toray reduced neither PGE_2 level in the pouch fluid 60 min after the injection of zymosan, nor vascular permeability increase during the period of 30 - 60 min. On the other hand, dexamethasone, a synthesized glucocorticoid, inhibited both responses potently and dose-dependently.(4) Lipocortin-Toray did not inhibit footpad edema induced by co-injection of histamine and PGE_2 in mice although dexamethasone and another synthesized glucocorticoid, betamethasone, inhibited it potently and dose-dependently.In conclusion, recombinant human lipocortin showed no significant anti-inflammatory activity. The anti-inflammatory activity of glucocorticoids can not be ascribed to the action of lipocortin.

脂皮质素被报道为一种抗炎蛋白，其介导糖皮质激素的抗炎作用。在该研究中，使用由Biogen Research Co.（lipocortin-Biogen）或Toray Industries Inc.（脂皮质素-东丽），我们旨在确定脂皮质素的抗炎活性是否与糖皮质激素的抗炎活性相当。(1)Lipocortin-Biogen以剂量依赖性方式抑制TPA诱导的[^3H]花生四烯酸标记的巨噬细胞释放放射性，但这种作用比地塞米松弱得多。(2)在高岭土诱导的气囊型炎症模型中，脂皮质素-Biogen在0 ~ 20 min内不能抑制血管通透性的增加，但在注射高岭土后20 min，气囊液中PGE_2含量呈剂量依赖性降低。(3)在酵母多糖诱导的气囊型炎症模型中，脂皮质素-东丽（Lipocortin-Toray）在注射酵母多糖后60 min内不降低气囊液中PGE_2的含量，在30 ~ 60 min内也不增加血管通透性，而地塞米松（一种合成的糖皮质激素）则有效地抑制这两种反应，并呈剂量依赖性。(4)Lipocortin Toray对组胺和PGE_2引起的小鼠足跖肿胀无明显抑制作用，而地塞米松和另一种合成的糖皮质激素则有明显的抑制作用，并呈剂量依赖性。糖皮质激素的抗炎活性不能归因于脂皮质素的作用。