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Piceatannol inhibits TNF-induced NF-kappaB activation and NF-kappaB-mediated gene expression through suppression of IkappaBalpha kinase and p65 phosphorylation.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Piceatannol inhibits TNF-induced NF-kappaB activation and NF-kappaB-mediated gene expression through suppression of IkappaBalpha kinase and p65 phosphorylation.
 
Creator Ashikawa, Kazuhiro
Majumdar, Sekhar
Banerjee, Sanjeev
Bharti, Alok C
Shishodia, Shishir
Aggarwal, Bharat B
 
Subject QR180 Immunology
 
Description Piceatannol is an anti-inflammatory, immunomodulatory, and anti-proliferative stilbene that has been shown to interfere with the cytokine signaling pathway. Previously, we have shown that resveratrol suppresses the activation of the nuclear transcription factor NF-kappaB. Piceatannol, previously reported as a selective inhibitor of protein tyrosine kinase Syk, is structurally homologous to resveratrol. Whether piceatannol can also suppress NF-kappaB activation was investigated. The treatment of human myeloid cells with piceatannol suppressed TNF-induced DNA binding activity of NF-kappaB. In contrast, stilbene or rhaponticin (another analog of piceatannol) had no effect, suggesting the critical role of hydroxyl groups. The effect of piceatannol was not restricted to myeloid cells, as TNF-induced NF-kappaB activation was also suppressed in lymphocyte and epithelial cells. Piceatannol also inhibited NF-kappaB activated by H(2)O(2), PMA, LPS, okadaic acid, and ceramide. Piceatannol abrogated the expression of TNF-induced NF-kappaB-dependent reporter gene and of matrix metalloprotease-9, cyclooxygenase-2, and cyclin D1. When examined for the mechanism, we found that piceatannol inhibited TNF-induced IkappaBalpha phosphorylation, p65 phosphorylation, p65 nuclear translocation, and IkappaBalpha kinase activation, but had no significant effect on IkappaBalpha degradation. Piceatannol inhibited NF-kappaB in cells with deleted Syk, indicating the lack of involvement of this kinase. Overall, our results clearly demonstrate that hydroxyl groups of stilbenes are critical and that piceatannol, a tetrahydroxystilbene, suppresses NF-kappaB activation induced by various inflammatory agents through inhibition of IkappaBalpha kinase and p65 phosphorylation.
 
Publisher American Association of Immunologists
 
Date 2002-12-01
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/886/1/majumdar2002..1.pdf
Ashikawa, Kazuhiro and Majumdar, Sekhar and Banerjee, Sanjeev and Bharti, Alok C and Shishodia, Shishir and Aggarwal, Bharat B (2002) Piceatannol inhibits TNF-induced NF-kappaB activation and NF-kappaB-mediated gene expression through suppression of IkappaBalpha kinase and p65 phosphorylation. Journal of immunology (Baltimore, Md. : 1950), 169 (11). pp. 6490-7. ISSN 0022-1767
 
Relation http://www.jimmunol.org/content/169/11/6490.full.pdf+html
http://crdd.osdd.net/open/886/