| Autor: |
Miller BE; Department of Inflammation Pharmacology, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, PA 19426., Krasney PA, Gauvin DM, Holbrook KB, Koonz DJ, Abruzzese RV, Miller RE, Pagani KA, Dolle RE, Ator MA, et. al. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1995 Feb 01; Vol. 154 (3), pp. 1331-8. |
| Abstrakt: |
The proinflammatory cytokine IL-1 beta is synthesized by activated monocytes and macrophages as a 31-kDa, biologically inactive precursor that is proteolytically processed to the biologically active 17-kDa mature molecule by the IL-1 beta converting enzyme (ICE). WIN 67694, Z-Val-Ala-Asp-CH2O(CO)[2,6-(CI2)]Ph, is a potent, selective inhibitor of human ICE. In activated murine peritoneal macrophages, WIN 67694 inhibited the release of mature IL-1 beta with an IC50 of 1.8 microM without any effect on the release of IL-1 alpha, IL-6, or TNF-alpha. The effect was specific to mature IL-1 beta release; the ICE inhibitor did not effect IL-1 beta RNA levels or precursor protein synthesis. In vivo, WIN 67694 was also able to inhibit selectively the release of IL-1 beta in a dose-dependent manner in a subcutaneous tissue chamber implant model of inflammation. IL-1 beta levels in tissue chamber fluid were inhibited 35 and 55% at 10 and 100 mg/kg, respectively. IL-1 alpha, IL-6, and TNF-alpha levels were not affected. The ability to selectively inhibit mature IL-1 beta release in vivo with ICE inhibitors will allow for detailed studies of the role of IL-1 beta and ICE in inflammatory diseases. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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