Curcumin (Diferulolylmethane) Reduces Transglutaminase 2 Overexpression Induced by Retinoic Acid in Human Nervous Cell Lines

Abstract Objectives: Curcumin, a naturally occurring compound derived from turmeric (Curcuma longa) has long been suggested to have strong therapeutic or preventive potential against human diseases because of its antioxidative, anticancerous, and anti-inflammatory effects. Curcumin is known to exert anti-inflammatory effects by interrupting NF-κB signaling at multiple levels. Many observations indicate that curcumin shows its valuable potential by inhibiting the activity of I-κB kinase. Transglutaminase 2 (TG2) expression is increased in inflammatory diseases. Data in the literature suggest that this enzyme activates the proinflammatory transcriptional factor NF-κB by inducing the polymerization of its inhibitory subunit I-κBα, which in turn results in the dissociation of NF- κB and its translocation to the nucleus, where it is capable of upregulating host inflammatory genes. Interestingly, NF-κB regulatory response elements are also present in the TG2 promoter, suggesting a possible role for this pathway in the mechanism responsible for chronic inflammation. On the basis of these literature data, our objective was to analyze the effects of curcumin on TG2 expression in human nervous cell lines. Methods: Human nervous cell lines were treated with curcumin alone or in association with retinoic acid in order to induce TG2 overexpression. TG2 levels were analyzed by Western blot and real-time PCR analyses. Results: Curcumin was able to downregulate the expression of TG2 in human nervous cell lines, which was also the case after treatment with retinoic acid. Conclusions: These results suggest a possible use of curcumin in reducing TG2 overexpression in human nervous cells.