| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B Activation Induced by TNF and H2O2, But Not That Activated by Ceramide, Lipopolysaccharides, or Phorbol Ester1
Cytokine Research Laboratory, Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
Thalidomide ([+]-
-phthalimidoglutarimide), a psychoactive drug
that readily crosses the blood-brain barrier, has been shown to exhibit
anti-inflammatory, antiangiogenic, and immunosuppressive properties
through a mechanism that is not fully established. Due to the central
role of NF-
B in these responses, we postulated that thalidomide
mediates its effects through suppression of NF-B activation. We
investigated the effects of thalidomide on NF-B activation induced
by various inflammatory agents in Jurkat cells. The treatment of these
cells with thalidomide suppressed TNF-induced NF-B activation, with
optimum effect occurring at 50 µg/ml thalidomide. These effects were
not restricted to T cells, as other hematopoietic and epithelial cell
types were also inhibited. Thalidomide suppressed
H2O2-induced NF-B activation but had no
effect on NF-B activation induced by PMA, LPS, okadaic acid, or
ceramide, suggesting selectivity in suppression of NF-B. The
suppression of TNF-induced NF-B activation by thalidomide correlated
with partial inhibition of TNF-induced degradation of an inhibitory
subunit of NF-B (IB), abrogation of IB kinase
activation, and inhibition of NF-B-dependent reporter gene
expression. Thalidomide abolished the NF-B-dependent reporter gene
expression activated by overexpression of TNFR1, TNFR-associated
factor-2, and NF-B-inducing kinase, but not that activated by the
p65 subunit of NF-B. Overall, our results clearly demonstrate that
thalidomide suppresses NF-B activation specifically induced by TNF
and H2O2 and that this may contribute to its
role in suppression of proliferation, inflammation, angiogenesis, and
the immune system.
This article has been cited by other articles:
|
|
 |
|
  B. Sung, A. B. Kunnumakkara, G. Sethi, P. Anand, S. Guha, and B. B. Aggarwal Curcumin circumvents chemoresistance in vitro and potentiates the effect of thalidomide and bortezomib against human multiple myeloma in nude mice model Mol. Cancer Ther., April 1, 2009; 8(4): 959 - 970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Aggarwal, R.V. Vijayalekshmi, and B. Sung Targeting Inflammatory Pathways for Prevention and Therapy of Cancer: Short-Term Friend, Long-Term Foe Clin. Cancer Res., January 15, 2009; 15(2): 425 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. C. Davel, L. E. Fukuda, L. L. De Sa, C. D. Munhoz, C. Scavone, D. Sanz-Rosa, V. Cachofeiro, V. Lahera, and L. V. Rossoni Effects of isoproterenol treatment for 7 days on inflammatory mediators in the rat aorta Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H211 - H219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bhardwaj, G. Sethi, S. Vadhan-Raj,, C. Bueso-Ramos, Y. Takada, U. Gaur, A. S. Nair, S. Shishodia, and B. B. Aggarwal Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-{kappa}B-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells Blood, March 15, 2007; 109(6): 2293 - 2302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ge, I. Montano, G. Rustici, W. J. Freebern, C. M. Haggerty, W. Cui, D. Ponciano-Jackson, G. V. R. Chandramouli, E. R. Gardner, W. D. Figg, et al. Selective leukemic-cell killing by a novel functional class of thalidomide analogs Blood, December 15, 2006; 108(13): 4126 - 4135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Lappas, Y.-J. Day, M. A. Marshall, V. H. Engelhard, and J. Linden Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation J. Exp. Med., November 27, 2006; 203(12): 2639 - 2648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. W. Maines, K. J. French, E. B. Wolpert, D. A. Antonetti, and C. D. Smith Pharmacologic Manipulation of Sphingosine Kinase in Retinal Endothelial Cells: Implications for Angiogenic Ocular Diseases Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5022 - 5031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Brown, M. McGuinness, T. Wright, X. Ren, Y. Wang, G. P. Boivin, H. Hahn, A. M. Feldman, and W. K. Jones Cardiac-specific blockade of NF-{kappa}B in cardiac pathophysiology: differences between acute and chronic stimuli in vivo Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H466 - H476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Abboushi, A. El-Hed, W. El-Assaad, L. Kozhaya, M. E. El-Sabban, A. Bazarbachi, R. Badreddine, A. Bielawska, J. Usta, and G. S. Dbaibo Ceramide Inhibits IL-2 Production by Preventing Protein Kinase C-Dependent NF-{kappa}B Activation: Possible Role in Protein Kinase C{theta} Regulation J. Immunol., September 1, 2004; 173(5): 3193 - 3200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-J. Park, H.-S. Kim, H.-M. Yang, K.-W. Park, S.-W. Youn, S.-I. Jeon, D.-H. Kim, B.-K. Koo, I.-H. Chae, D.-J. Choi, et al. Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia After Balloon Injury in Rat Carotid Artery Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 885 - 891. [Abstract] [Full Text]
|
|
|
|
|
|
H. R. Gockel, A. Lugering, J. Heidemann, M. Schmidt, W. Domschke, T. Kucharzik, and N. Lugering Thalidomide Induces Apoptosis in Human Monocytes by Using a Cytochrome c-Dependent Pathway J. Immunol., April 15, 2004; 172(8): 5103 - 5109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Bharti, S. Shishodia, J. M. Reuben, D. Weber, R. Alexanian, S. Raj-Vadhan, Z. Estrov, M. Talpaz, and B. B. Aggarwal Nuclear factor-{kappa}B and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis Blood, April 15, 2004; 103(8): 3175 - 3184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hess, N. Wijayanti, A. P. Neuschafer-Rube, N. Katz, T. Kietzmann, and S. Immenschuh Phorbol Ester-dependent Activation of Peroxiredoxin I Gene Expression via a Protein Kinase C, Ras, p38 Mitogen-activated Protein Kinase Signaling Pathway J. Biol. Chem., November 14, 2003; 278(46): 45419 - 45434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shishodia, P. Potdar, C. G. Gairola, and B. B. Aggarwal Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-{kappa}B activation through inhibition of I{kappa}B{alpha} kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1 Carcinogenesis, July 1, 2003; 24(7): 1269 - 1279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. H. Schafer, A. K. Gandhi, M. A. Loveland, R. S. Chen, H.-W. Man, P. P. M. Schnetkamp, G. Wolbring, S. Govinda, L. G. Corral, F. Payvandi, et al. Enhancement of Cytokine Production and AP-1 Transcriptional Activity in T Cells by Thalidomide-Related Immunomodulatory Drugs J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1222 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wu, M. Marko, K. Claycombe, K. E. Paulson, and S. N. Meydani Ceramide-induced and Age-associated Increase in Macrophage COX-2 Expression Is Mediated through Up-regulation of NF-kappa B Activity J. Biol. Chem., March 21, 2003; 278(13): 10983 - 10992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Rajkumar, S. Hayman, M. A. Gertz, A. Dispenzieri, M. Q. Lacy, P. R. Greipp, S. Geyer, N. Iturria, R. Fonseca, J. A. Lust, et al. Combination Therapy With Thalidomide Plus Dexamethasone for Newly Diagnosed Myeloma J. Clin. Oncol., November 1, 2002; 20(21): 4319 - 4323. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
