Studies on the anti-inflammatory action of acute-phase proteinase inhibitors in rats
| Project/Area Number |
62570978
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
NAKAGAWA Hideo Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Professor, 薬学部, 教授 (00012617)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1987: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Acute-phase reactants / Proteinase inhibitors / Acute-phase proteinase inhibitors / Anti-inflammatory action / Chemotaxis / Neutrophil chemotactic factor / Vascular permeability / 線維芽細胞 / ゼラチナーゼ / 多形核白血球の化学遊走 |
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| Research Abstract |
_2 Acute-phase macroglobulin ( _2APM), _1 proteinase inhibitor ( _1PI) and cysteineproteinase inhibitors (CPIs) are present at high concentration in the 24-h serum and known as acute-phase reactants in rats. In the present studies, acute-phase proteinase inhibitors were purified from inflamed rat serum or exudate and effect of the purified inhibitors on inflammatory processes was studied. The results obtained as follows:
1. _2APM, _1PI, CPI-1 and CPI-2 have been purified to homogeneity from 24-h serum or day-7 exudate.
2. Effect of the purified proteinase inhibitors on PMN chemotaxis was studied by Boyden's method in vitro. _2APM (4 mg/ml) and _1PI (1 and 3 mg/ml) significantly suppressed PMN chemotaxis, whereas CPI-1 and CPI-i had no inhibitory effect. These results suggest that _2APM and _1PI play a role in suppression of PMNs infiltration into the inflammatory site in the late-phase of acute inflammation.
3. Serotonin-mediated vascular permeability was not suppressed by _2APM, _1M and CPIs, suggesting that the inhibitors had no effect on vascular permeability in acute-phase of inflammation.
4. Plasms concentrations of _2APM, _1M and CPIs markedly increased inthe acute phase and a high concentration of plasma and exudate cpis was found furing the chronic phase, whereas plasma concentrations of _2APM and _1PI rapidly decreased. Therefore, the effect of CPIs on the production of gelatinase and neutrophil chemotactic factor by granulation tissue-derived fibroblasts was studied in vitro. Both CPI-1 and CPI-2 enhanced the production of gelatinase and neutrophil chemotactic factor in a dose-dependent manner, suggesting that CPIs activate the fibroblasts to produce inflammatory mediators including proteinases and neutrophil chemoattractants.
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Report
(3 results)
Research Products
(4 results)
