PT - JOURNAL ARTICLE AU - Huang, Shurong AU - Zhao, Ling AU - Kim, Kihoon AU - Lee, Dong Seok AU - Hwang, Daniel H. TI - Inhibition of Nod2 Signaling and Target Gene Expression by Curcumin AID - 10.1124/mol.108.046169 DP - 2008 Jul 01 TA - Molecular Pharmacology PG - 274--281 VI - 74 IP - 1 4099 - http://molpharm.aspetjournals.org/content/74/1/274.short 4100 - http://molpharm.aspetjournals.org/content/74/1/274.full SO - Mol Pharmacol2008 Jul 01; 74 AB - Nod2 is an intracellular pattern recognition receptor that detects a conserved moiety of bacterial peptidoglycan and subsequently activates proinflammatory signaling pathways. Mutations in Nod2 have been implicated to be linked to inflammatory granulomatous disorders, such as Crohn's disease and Blau syndrome. Many phytochemicals possess anti-inflammatory properties. However, it is not known whether any of these phytochemicals might modulate Nod2-mediated immune responses and thus might be of therapeutic value for the intervention of these inflammatory diseases. In this report, we demonstrate that curcumin, a polyphenol found in the plant Curcuma longa, and parthenolide, a sesquiterpene lactone, suppress both ligand-induced and lauric acid-induced Nod2 signaling, leading to the suppression of nuclear factor-κB activation and target gene interleukin-8 expression. We provide molecular and biochemical evidence that the suppression is mediated through the inhibition of Nod2 oligomerization and subsequent inhibition of downstream signaling. These results demonstrate for the first time that curcumin and parthenolide can directly inhibit Nod2-mediated signaling pathways at the receptor level and suggest that Nod2-mediated inflammatory responses can be modulated by these phytochemicals. It remains to be determined whether these phytochemicals possess protective or therapeutic efficacy against Nod2-mediated inflammatory disorders. The American Society for Pharmacology and Experimental Therapeutics