Curcumin blocks cytokine-mediated NF-?B activation and proinflammatory gene expression by inhibiting inhibitory factor I-?B kinase activity

Document Type

Article

Publication Date

9-15-1999

Abstract

NF-?B plays a critical role in the transcriptional regulation of proinflammatory gene expression in various cells. Cytokine-mediated activation of NF-?B requites activation of various kinases, which ultimately leads to the phosphorylation and degradation of I?B, the NF-?B cytoplasmic inhibitor. The food derivative curcumin has been shown to inhibit NF-?B activity in some cell types. In this report we investigate the mechanism of action of curcumin on cytokine-induced proinflammatory gene expression using intestinal epithelial cells (IEC). Curcumin inhibited IL-1?-mediated ICAM-1 and IL-8 gene expression in IEC-6, HT-29, and Caco-2 cells. Cytokine-induced NF-?B DNA binding activity, RelA nuclear translocation, I?B? degradation, I?B serine 32 phosphorylation, and bob kinase (IKK) activity were blocked by curcumin treatment. Wound-induced p38 phosphorylation was not inhibited by curcumin treatment. In addition, mitogen-activated protein kinase/ERK kinase kinase-1-induced IL-8 gene expression and 12-O-tetraphorbol 12-myristate 13- acetate-responsive element-driven luciferase expression were inhibited by curcumin. However, I?B? degradation induced by ectopically expressed NF- ?B-inducing kinase or IKK was not inhibited by curcumin treatment. Therefore, curcumin blocks a signal upstream of NF-?B-inducing kinase and IKK. We conclude that curcumin patently inhibits cytokine-mediated NF-?B activation by blocking a signal leading to IKK activity.

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