1989 Fiscal Year Final Research Report Summary
Comparison of anti-inflammatory activities between recombinant human lipocortin and glucocorticoid.
| Project/Area Number |
62870092
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
OHUCHI Kazuo Tohoku University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20006357)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Yumiko Tohoku University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 教務職員 (70167469)
HIRASAWA Noriyasu Tohoku University, Faculty of Pharmaceutical Sciences, Assist. Prof., 薬学部, 助手 (80181155)
WATANABE Masako Tohoku University, Faculty of Pharmaceutical Sciences, Assit. Prof., 薬学部, 助手 (90182948)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Lipocortin / Glucocorticoid / Anti-inflammatory drugs / Phospholipase / Arachidonic acid / Prostaglandin / Vascular permeability / Footpad edema |
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| Research Abstract |
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.
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