|
|
||||||||
B Activation and NF-
B-Mediated Gene Expression Through Suppression of I
B
Kinase and p65 Phosphorylation1
Cytokine Research Laboratory, Department of Bioimmunotherapy, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030
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-
B. Piceatannol, previously reported as a selective
inhibitor of protein tyrosine kinase Syk, is structurally homologous to
resveratrol. Whether piceatannol can also suppress NF-
B activation
was investigated. The treatment of human myeloid cells with piceatannol
suppressed TNF-induced DNA binding activity of NF-
B. 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-
B
activation was also suppressed in lymphocyte and epithelial cells.
Piceatannol also inhibited NF-
B activated by
H2O2, PMA, LPS, okadaic acid, and ceramide.
Piceatannol abrogated the expression of TNF-induced NF-
B-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 I
B
phosphorylation, p65 phosphorylation,
p65 nuclear translocation, and I
B
kinase activation, but had no
significant effect on I
B
degradation. Piceatannol inhibited
NF-
B 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-
B activation induced by various
inflammatory agents through inhibition of I
B
kinase and p65
phosphorylation.
This article has been cited by other articles:
![]() |
A. C. Klimowicz, S. A. Bisson, K. Hans, E. M. Long, H. C. Hansen, and S. M. Robbins The phytochemical piceatannol induces the loss of CBL and CBL-associated proteins Mol. Cancer Ther., March 1, 2009; 8(3): 602 - 614. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. Bijli, F. Fazal, M. Minhajuddin, and A. Rahman Activation of Syk by Protein Kinase C-{delta} Regulates Thrombin-induced Intercellular Adhesion Molecule-1 Expression in Endothelial Cells via Tyrosine Phosphorylation of RelA/p65 J. Biol. Chem., May 23, 2008; 283(21): 14674 - 14684. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Waldeck-Weiermair, C. Zoratti, K. Osibow, N. Balenga, E. Goessnitzer, M. Waldhoer, R. Malli, and W. F. Graier Integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression J. Cell Sci., May 15, 2008; 121(10): 1704 - 1717. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Ungvari, Z. Orosz, A. Rivera, N. Labinskyy, Z. Xiangmin, S. Olson, A. Podlutsky, and A. Csiszar Resveratrol increases vascular oxidative stress resistance Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2417 - H2424. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Gilbert, C. Barat, R. Cantin, and M. J. Tremblay Involvement of Src and Syk Tyrosine Kinases in HIV-1 Transfer from Dendritic Cells to CD4+ T Lymphocytes J. Immunol., March 1, 2007; 178(5): 2862 - 2871. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. S. Ahn, G. Sethi, K. Krishnan, and B. B. Aggarwal {gamma}-Tocotrienol Inhibits Nuclear Factor-{kappa}B Signaling Pathway through Inhibition of Receptor-interacting Protein and TAK1 Leading to Suppression of Antiapoptotic Gene Products and Potentiation of Apoptosis J. Biol. Chem., January 5, 2007; 282(1): 809 - 820. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. David, A. Saez-Cirion, P. Versmisse, O. Malbec, B. Iannascoli, F. Herschke, M. Lucas, F. Barre-Sinoussi, J.-F. Mouscadet, M. Daeron, et al. The Engagement of Activating Fc{gamma}Rs Inhibits Primate Lentivirus Replication in Human Macrophages J. Immunol., November 1, 2006; 177(9): 6291 - 6300. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Csiszar, K. Smith, N. Labinskyy, Z. Orosz, A. Rivera, and Z. Ungvari Resveratrol attenuates TNF-{alpha}-induced activation of coronary arterial endothelial cells: role of NF-{kappa}B inhibition. Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1694 - H1699. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Pilling, N. M. Tucker, and R. H. Gomer Aggregated IgG inhibits the differentiation of human fibrocytes J. Leukoc. Biol., June 1, 2006; 79(6): 1242 - 1251. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Ray, M. Kuwahara, Y. Takada, K. Maruyama, T. Kawaguchi, H. Tsubone, H. Ishikawa, and K. Matsuo c-Fos suppresses systemic inflammatory response to endotoxin Int. Immunol., May 1, 2006; 18(5): 671 - 677. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Takada, H. Ichikawa, V. Badmaev, and B. B. Aggarwal Acetyl-11-Keto-beta-Boswellic Acid Potentiates Apoptosis, Inhibits Invasion, and Abolishes Osteoclastogenesis by Suppressing NF-{kappa}B and NF-{kappa}B-Regulated Gene Expression. J. Immunol., March 1, 2006; 176(5): 3127 - 3140. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. R. Martin Targeting Apoptosis with Dietary Bioactive Agents Experimental Biology and Medicine, February 1, 2006; 231(2): 117 - 129. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Sekine, T. Yumioka, T. Yamamoto, R. Muromoto, S. Imoto, K. Sugiyma, K. Oritani, K. Shimoda, M. Minoguchi, S. Akira, et al. Modulation of TLR4 Signaling by a Novel Adaptor Protein Signal-Transducing Adaptor Protein-2 in Macrophages J. Immunol., January 1, 2006; 176(1): 380 - 389. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. S. Youn, J. Y. Lee, K. A. Fitzgerald, H. A. Young, S. Akira, and D. H. Hwang Specific Inhibition of MyD88-Independent Signaling Pathways of TLR3 and TLR4 by Resveratrol: Molecular Targets Are TBK1 and RIP1 in TRIF Complex J. Immunol., September 1, 2005; 175(5): 3339 - 3346. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Yang, C. Lin, and Z.-R. Liu Phosphorylations of DEAD Box p68 RNA Helicase Are Associated with Cancer Development and Cell Proliferation Mol. Cancer Res., June 1, 2005; 3(6): 355 - 363. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ulanova, L. Puttagunta, M. Marcet-Palacios, M. Duszyk, U. Steinhoff, F. Duta, M.-K. Kim, Z. K. Indik, A. D. Schreiber, and A. D. Befus Syk tyrosine kinase participates in {beta}1-integrin signaling and inflammatory responses in airway epithelial cells Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L497 - L507. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Takada and B. B. Aggarwal Evidence that genetic deletion of the TNF receptor p60 or p80 in macrophages modulates RANKL-induced signaling Blood, December 15, 2004; 104(13): 4113 - 4121. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Storz, H. Doppler, and A. Toker Activation Loop Phosphorylation Controls Protein Kinase D-Dependent Activation of Nuclear Factor {kappa}B Mol. Pharmacol., October 1, 2004; 66(4): 870 - 879. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Takada and B. B. Aggarwal TNF Activates Syk Protein Tyrosine Kinase Leading to TNF-Induced MAPK Activation, NF-{kappa}B Activation, and Apoptosis J. Immunol., July 15, 2004; 173(2): 1066 - 1077. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Takada, F. R. Khuri, and B. B. Aggarwal Protein Farnesyltransferase Inhibitor (SCH 66336) Abolishes NF-{kappa}B Activation Induced by Various Carcinogens and Inflammatory Stimuli Leading to Suppression of NF-{kappa}B-regulated Gene Expression and Up-regulation of Apoptosis J. Biol. Chem., June 18, 2004; 279(25): 26287 - 26299. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Takada, S. Singh, and B. B. Aggarwal Identification of a p65 Peptide That Selectively Inhibits NF-{kappa} B Activation Induced by Various Inflammatory Stimuli and Its Role in Down-regulation of NF-{kappa}B-mediated Gene Expression and Up-regulation of Apoptosis J. Biol. Chem., April 9, 2004; 279(15): 15096 - 15104. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. PERVAIZ Resveratrol: from grapevines to mammalian biology FASEB J, November 1, 2003; 17(14): 1975 - 1985. [Full Text] [PDF] |
||||
![]() |
Y. Takada and B. B. Aggarwal Betulinic Acid Suppresses Carcinogen-Induced NF-{kappa}B Activation Through Inhibition of I{kappa}B{alpha} Kinase and p65 Phosphorylation: Abrogation of Cyclooxygenase-2 and Matrix Metalloprotease-9 J. Immunol., September 15, 2003; 171(6): 3278 - 3286. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Takada and B. B. Aggarwal Genetic Deletion of the Tumor Necrosis Factor Receptor p60 or p80 Sensitizes Macrophages to Lipopolysaccharide-induced Nuclear Factor-{kappa}B, Mitogen-activated Protein Kinases, and Apoptosis J. Biol. Chem., June 20, 2003; 278(26): 23390 - 23397. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |