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In murine osteoblastic MC3T3-E1 cells which produced prostaglandin E2 as a bone resorption factor, the cyclooxygenase-2 induction by tumor necrosis factor K K (TNFK K) was suppressed by dexamethasone with an IC 50 of 1 nM. Humulon isolated from hop extract for beer brewing was reported previously as an inhibitor of bone resorption [Tobe, H. et al. (1997) Biosci. Biotech. Biochem. 61, 158^159]. We showed that the compound suppressed the TNFK K-dependent cyclooxygenase-2 induction with an IC 50 of as low as about 30 nM as demonstrated experimentally by catalytic activity assay, Northern blot analysis and promoter analysis. Reporter gene experiments suggested that humulon blocked the cyclooxygenase-2 expression mediated by NFU UB and NF-IL6, but the intracellular glucocorticoid receptor was not involved. The catalytic activity of cyclooxygenase-2 was inhibited by humulon with an IC 50 of as high as 1.6 W WM. These results showed that humulon suppressed cyclooxygenase-2 induction at the step of transcription.z 2000 Federation of European Biochemical Societies.

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