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РЖ ВИНИТИ 76 (BI31) 96.09-04Т3.494

Rainsford, K. D.
Effects of 5-lipoxygenase inhibitors on interleukin production by human synovial tissues in organ culture: Comparison with interleukin-1-synthesis inhibitors [Text] / K. D. Rainsford, C. Ying, F. Smith // J. Pharm. and Pharmacol. - 1996. - Vol. 48, N 1. - P46-52 . - ISSN 0022-3573
Перевод заглавия: Влияние ингибиторов 5-липоксигеназы на продукцию интерлейкина в органной культуре человеческой синовиальной ткани: сравнение с ингибиторами синтеза интерлейкина-1
Аннотация: Prostaglandins and leukotrienes differentially regulate the production of interleukin-1 (IL-1) in monocytes. It was, therefore, decided to investigate the effects of some 5-lipoxygenase inhibitors compared with standard IL-1-synthesis inhibitors on the production of IL-1 by human synovial tissue explants in organ culture. Human synovial (from hip/knee arthroplasty) or porcine tibio-tarsal joint synovial explants were incubated in organ culture in Dulbecco's Modified Eagle's Medium + 5% foetal calf serum in the presence of the test compounds or solvents (controls), or media alone for 1-5 days. Total bioactive IL-1 was assayed in the medium (following serial dilution or with polyethylene glycol 8000 added in some assays to remove inhibitors) using the D-10 T-cell bioassay. Some assays of interleukins 1'альфа', 1'бета', 6 or 8 were performed by ELISA. Of the 5-lipoxygenase inhibitors investigated, MK886 (3-(1-(4-chlorobenzyl)-3-tert-butyl-thio-5-isopropylindol-2-yl)-2,2- dimethyl propanoic acid), L-656,224 ((7-chloro-2-[4-methoxypenyl]methyl)-3-methyl-5-propyl-4-benzofuranol), PF-5901 and tepoxalin were the most potent inhibitors of IL-1 production. While the PF-5901 was effective at 5-30 'мю'm and tepoxalin was effective at 1-10 'мю'm, the others were the most potent having minimal inhibitory activity in the range of 0,01-0,1 'мю'm. The presumed IL-1-synthesis inhibitors, tenidap and IX-207,887, were ingactive at concentrations of 30-50 'мю'm. Leгkоtriene B[4] (1-100 ng mL{-1}) added to MK-886 (5 'мю'm)-treated cultures reversed the inhibitory effects of the latter on IL-1, confirming the role of 5-lipoxygenase products in the regulation of IL-1 production. Addition of polyethylene glycol 8000 to MK-886-treated cultures climinated the inhibitory ellects of this drug, suggesting that this drug exerts its effects by promoting production of IL-1 inhibitors. MK-886 also inhibited synovial production of two other pleiotrophic cytokines which it regulates, IL-6 and IL-8. The results suggest that some 5-lipoxygenase inhibitors may be usefully employed in regulating production of those interleukins involved in joint cartilage destruction. Библ. 35

ГРНТИ	76.31.29

ВИНИТИ 761.31.29.41.11
Рубрики: ЛИПОКСИГЕНАЗЫ ИНГИБИТОРЫ
ХИРУРГИЧЕСКИЕ ОПЕРАЦИИ
ЧЕЛОВЕЧЕСКАЯ СИНОВИАЛЬНАЯ ОБОЛОЧКА
ОРГАННАЯ КУЛЬТУРА
ПРОДУКЦИЯ ИНТЕРЛЕЙКИНА-1
АРТРОПЛАСТИКА БЕДРА
АРТРОПЛАСТИКА КОЛЕНА
БОЛЬНЫЕ

Доп.точки доступа:
Ying, C.; Smith, F.

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