期刊
MOLECULAR NUTRITION & FOOD RESEARCH
卷 53, 期 11, 页码 1386-1395出版社
WILEY
DOI: 10.1002/mnfr.200800583
关键词
CCAAT/enhancer-binding protein beta; Cyclooxygenase-2 (COX-2); Inducible NO synthase (iNOS); Inotilone; LPS
资金
- National Science Council of Taiwan [NSC 97-2321-B-022-001, NSC 95-2313-B-022-003-MY3]
The inhibitory effects of inotilone and methylinotilone on the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with LPS were investigated. The results show that both hydroxyl groups on the benzene ring of the inotilone molecule are required for better anti-inflammatory effect. Western blotting and RTPCR analyses demonstrated that inotilone blocked protein and mRNA expression of iNOS but not COX-2. Instead, inotilone inhibited prostaglandin EZ production through decreasing the enzyme activity of COX-2. The repression of iNOS but not COX-2 expression may come from the differential effect of inotilone on nuclear factor-kappa B (NF kappa B) and CCAAT/enhancer-binding protein beta Treatment with inotilone resulted in the reduction of LPS-induced nuclear translocation of NF kappa B subunit and the NF kappa B-dependent transcriptional activity by blocking phosphorylation of inhibitor kappa B(I kappa B)alpha and p65 and subsequent degradation of inhibitor kappa B alpha. Inotilone also inhibited LPS-induced activation of PI3K/Akt and extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase. Our results suggest that inotilone may have potential to be developed into an effective anti-inflammatory agent.
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