| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Induction in Monocytes by Direct Interaction with I
B Kinases1
Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Ulm, Germany
Expression of proinflammatory cytokines by monocytes is tightly regulated by transcription factors such as NF-
B. In this study, we show that, in LPS-stimulated human peripheral monocytes, the pentacyclic triterpenes acetyl-
-boswellic acid (ABA) and acetyl-11-keto-
-boswellic acid (AKBA) down-regulate the TNF- expression. ABA and AKBA inhibited NF-B signaling both in LPS-stimulated monocytes as detected by EMSA, as well as in a NF-B-dependent luciferase gene reporter assay. By contrast, the luciferase expression driven by the IFN-stimulated response element was unaffected, implying specificity of the inhibitory effect observed. Both ABA and AKBA did not affect binding of recombinant p50/p65 and p50/c-Rel dimers to DNA binding sites as analyzed by surface plasmon resonance. Instead, both pentacyclic triterpenes inhibited the LPS-induced degradation of IB, as well as phosphorylation of p65 at Ser536 and its nuclear translocation. ABA and AKBA inhibited specifically the phosphorylation of recombinant IB and p65 by IB kinases (IKKs) immunoprecipitated from LPS-stimulated monocytes. In line with this, ABA and AKBA also bound to and inhibited the activities of active human recombinant GST-IKK and His-IKK. The LPS-triggered induction of TNF- in monocytes is dependent on IKK activity, as confirmed by IKK-specific antisense oligodeoxynucleotides. Thus, via their direct inhibitory effects on IKK, ABA and AKBA convey inhibition of NF-B and subsequent down-regulation of TNF- expression in activated human monocytes. These findings provide a molecular basis for the anti-inflammatory properties ascribed to ABA- and AKBA-containing drugs and suggest acetyl-boswellic acids as tools for the development of novel therapeutic interventions.
This article has been cited by other articles:
|
|
 |
|
  A. B. Kunnumakkara, A. S. Nair, B. Sung, M. K. Pandey, and B. B. Aggarwal Boswellic Acid Blocks Signal Transducers and Activators of Transcription 3 Signaling, Proliferation, and Survival of Multiple Myeloma via the Protein Tyrosine Phosphatase SHP-1 Mol. Cancer Res., January 1, 2009; 7(1): 118 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Popovic, Y. Laumonnier, L. Burysek, T. Syrovets, and T. Simmet Thrombin-induced expression of endothelial CX3CL1 potentiates monocyte CCL2 production and transendothelial migration J. Leukoc. Biol., July 1, 2008; 84(1): 215 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Kruger, R. Daneshfar, G. P. Eckert, J. Klein, D. A. Volmer, U. Bahr, W. E. Muller, M. Karas, M. Schubert-Zsilavecz, and M. Abdel-Tawab Metabolism of Boswellic Acids in Vitro and in Vivo Drug Metab. Dispos., June 1, 2008; 36(6): 1135 - 1142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cuaz-Perolin, L. Billiet, E. Bauge, C. Copin, D. Scott-Algara, F. Genze, B. Buchele, T. Syrovets, T. Simmet, and M. Rouis Antiinflammatory and Antiatherogenic Effects of the NF-{kappa}B Inhibitor Acetyl-11-Keto-{beta}-Boswellic Acid in LPS-Challenged ApoE-/- Mice Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 272 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Wieser, M. Cohen, A. Gaeddert, J. Yu, C. Burks-Wicks, S. L. Berga, and R. N. Taylor Evolution of medical treatment for endometriosis: back to the roots? Hum. Reprod. Update, September 1, 2007; 13(5): 487 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, Y. Laumonnier, T. Syrovets, and T. Simmet Plasmin Triggers Cytokine Induction in Human Monocyte-Derived Macrophages Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1383 - 1389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Poeckel, L. Tausch, N. Kather, J. Jauch, and O. Werz Boswellic Acids Stimulate Arachidonic Acid Release and 12-Lipoxygenase Activity in Human Platelets Independent of Ca2+ and Differentially Interact with Platelet-Type 12-Lipoxygenase Mol. Pharmacol., September 1, 2006; 70(3): 1071 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vojdani and J. Erde Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers: The Ultimate Antagonist (I). Evid. Based Complement. Altern. Med., March 1, 2006; 3(1): 25 - 30. [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]
|
|
|
|
 |
|
 D. Poeckel, L. Tausch, S. George, J. Jauch, and O. Werz 3-O-Acetyl-11-keto-boswellic Acid Decreases Basal Intracellular Ca2+ Levels and Inhibits Agonist-Induced Ca2+ Mobilization and Mitogen-Activated Protein Kinase Activation in Human Monocytic Cells J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 224 - 232. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
