1989 Fiscal Year Final Research Report Summary
Mechanisms for anti-inflammatory actions of glucocorticoid
| Project/Area Number |
63480460
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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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, Assit. Prof., 薬学部, 助手 (80181155)
WATANABE Masako Tohoku University, Faculty of Pharmaceutical Sciences, Assit. Prof., 薬学部, 助手 (90182948)
WADA Yumiko Tohoku University, Faculty of Pharmaceutical Sciences, Instructor (70167469)
WADA Yumiko Tohoku University, Faculty of Pharmaceutical Sciences, Instructor (70167469)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Glucocorticoid / Vascular permeability / Neutrophil infiltration / Peptide-leukotriene / Chemotactic factor |
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| Research Abstract |
Mechanisms for the anti-inflammatory actions of glucocorticoid were studied using several air pouch type inflammation models. (1) Injection of 1.6 %$(w/v) zymosan in 0.8 % (w/v) CMC-Na solution into the air pouch induced increases in the levels of prostaglandin E_2 (PGE_2) and peptide-leukotrienes (LTs) in the pouch fluid at 1 hr.
Administration of a 5-lipoxygenase inhibitor, AA861, at time 0 or dexamethasone 3 hr before the zymosan injection reduced both PGE_2 levels and peptide-LTs levels in the pouch fluid at 1 hr. Although these effects of dexamethasone were weaker than those of AA861, the inhibitory effect of dexamethasone on the vascular permeability response during the period from 0.5 to 1 hr was stronger than that of AA861. (2) Lipopolysaccharide-induced increases in neutrophil accumulation and chemotactic activity in the pouch fluid at 4 hr were inhibited by actinomycin D but not by AA861. Dexamethasone reduced the chemotactic activity and the number of neutrophils infiltrated in the pouch fluid 4 hr after the LPS injection. (3) Pretreatment of dexamethasone inhibited zymosan-activated serum-induced neutrophil infiltration during the first 1 hr without reducing the chemotactic activity in the pouch fluid. These results suggest that dexamethasone inhibits vascular permeability response and neutrophil infiltration by another mechanism than phospholipase A_2 inhibition. Inhibition of neutrophil infiltration by dexamethasone is ascribed to the inhibition of both the production of protein-like chemotactic factor and the responses of neutrophil and/or vascular endothelial cells to chemotactic factors. In conclusion, the inhibitory action of glucocorticoid on phospholipase A_2 is not the main mechanism for anti-inflammatory effects of glucocorticoid.
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