This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schwenger, P.
Right arrow Articles by Vilcek, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schwenger, P.
Right arrow Articles by Vilcek, J.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Jan 1998, 78-84, Vol 18, No. 1
Copyright © 1998, American Society for Microbiology

Activation of p38 mitogen-activated protein kinase by sodium salicylate leads to inhibition of tumor necrosis factor-induced IkappaB alpha phosphorylation and degradation

P Schwenger, D Alpert, EY Skolnik and J Vilcek
Department of Microbiology, Skirball Institute for Biomolecular Medicine, NYU Medical Center, New York 10016, USA.

Many actions of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) on gene expression are mediated by the transcription factor NF-kappaB. Activation of NF-kappaB by TNF and IL-1 is initiated by the phosphorylation of the inhibitory subunit, IkappaB, which targets IkappaB for degradation and leads to the release of active NF-kappaB. The nonsteroidal anti-inflammatory drug sodium salicylate (NaSal) interferes with TNF-induced NF-kappaB activation by inhibiting phosphorylation and subsequent degradation of the IkappaB alpha protein. Recent evidence indicated that NaSal activates the p38 mitogen-activated protein kinase (MAPK), raising the possibility that inhibition of NF-kappaB activation by NaSal is mediated by p38 MAPK. We now show that inhibition of TNF-induced IkappaB alpha phosphorylation and degradation by NaSal is prevented by treatment of cells with SB203580, a highly specific p38 MAPK inhibitor. Both p38 activation and inhibition of TNF-induced IkappaB alpha degradation were seen after only 30 s to 1 min of NaSal treatment. Induction of p38 MAPK activation and inhibition of TNF-induced IkappaB alpha degradation were demonstrated with pharmacologically achievable doses of NaSal. These findings provide evidence for a role of NaSal-induced p38 MAPK activation in the inhibition of TNF signaling and suggest a possible role for the p38 MAPK in the anti-inflammatory actions of salicylates. In addition, these results implicate the p38 MAPK as a possible negative regulator of TNF signaling that leads to NF-kappaB activation.


This article has been cited by other articles:

  • Fang, X., Feng, Y., Shi, Z., Dai, J. (2009). Alterations of Cytokines and MAPK Signaling Pathways are Related to the Immunotoxic Effect of Perfluorononanoic Acid. Toxicol Sci 108: 367-376 [Abstract] [Full Text]  
  • Sapienza, K., Bannister, W., Balzan, R. (2008). Mitochondrial involvement in aspirin-induced apoptosis in yeast. Microbiology 154: 2740-2747 [Abstract] [Full Text]  
  • D'Alimonte, I., Flati, V., D'Auro, M., Toniato, E., Martinotti, S., Rathbone, M. P., Jiang, S., Ballerini, P., Di Iorio, P., Caciagli, F., Ciccarelli, R. (2007). Guanosine Inhibits CD40 Receptor Expression and Function Induced by Cytokines and beta Amyloid in Mouse Microglia Cells. J. Immunol. 178: 720-731 [Abstract] [Full Text]  
  • Derouet, M., Thomas, L., Moulding, D. A., Akgul, C., Cross, A., Moots, R. J., Edwards, S. W. (2006). Sodium Salicylate Promotes Neutrophil Apoptosis by Stimulating Caspase-Dependent Turnover of Mcl-1. J. Immunol. 176: 957-965 [Abstract] [Full Text]  
  • Mishra, S., Mishra, J. P., Gee, K., McManus, D. C., LaCasse, E. C., Kumar, A. (2005). Distinct Role of Calmodulin and Calmodulin-dependent Protein Kinase-II in Lipopolysaccharide and Tumor Necrosis Factor-{alpha}-mediated Suppression of Apoptosis and Antiapoptotic c-IAP2 Gene Expression in Human Monocytic Cells. J. Biol. Chem. 280: 37536-37546 [Abstract] [Full Text]  
  • Ariyoshi, W., Takahashi, T., Kanno, T., Ichimiya, H., Takano, H., Koseki, T., Nishihara, T. (2005). Mechanisms Involved in Enhancement of Osteoclast Formation and Function by Low Molecular Weight Hyaluronic Acid. J. Biol. Chem. 280: 18967-18972 [Abstract] [Full Text]  
  • Orr, A. W., Sanders, J. M., Bevard, M., Coleman, E., Sarembock, I. J., Schwartz, M. A. (2005). The subendothelial extracellular matrix modulates NF-{kappa}B activation by flow: a potential role in atherosclerosis. JCB 169: 191-202 [Abstract] [Full Text]  
  • Wu, D., Cederbaum, A. (2004). Glutathione Depletion in CYP2E1-Expressing Liver Cells Induces Toxicity Due to the Activation of p38 Mitogen-Activated Protein Kinase and Reduction of Nuclear Factor-{kappa}B DNA Binding Activity. Mol. Pharmacol. 66: 749-760 [Abstract] [Full Text]  
  • Mifflin, R. C., Saada, J. I., Di Mari, J. F., Valentich, J. D., Adegboyega, P. A., Powell, D. W. (2004). Aspirin-Mediated COX-2 Transcript Stabilization via Sustained p38 Activation in Human Intestinal Myofibroblasts. Mol. Pharmacol. 65: 470-478 [Abstract] [Full Text]  
  • Pillinger, M. H., Rosenthal, P. B., Tolani, S. N., Apsel, B., Dinsell, V., Greenberg, J., Chan, E. S. L., Gomez, P. F., Abramson, S. B. (2003). Cyclooxygenase-2-Derived E Prostaglandins Down-Regulate Matrix Metalloproteinase-1 Expression in Fibroblast-Like Synoviocytes via Inhibition of Extracellular Signal-Regulated Kinase Activation. J. Immunol. 171: 6080-6089 [Abstract] [Full Text]  
  • Weber, N. C., Blumenthal, S. B., Hartung, T., Vollmar, A. M., Kiemer, A. K. (2003). ANP inhibits TNF-{alpha}-induced endothelial MCP-1 expression--involvement of p38 MAPK and MKP-1. J. Leukoc. Biol. 74: 932-941 [Abstract] [Full Text]  
  • Yoon, J.-B., Kim, S.-J., Hwang, S.-G., Chang, S., Kang, S.-S., Chun, J.-S. (2003). Non-steroidal Anti-inflammatory Drugs Inhibit Nitric Oxide-induced Apoptosis and Dedifferentiation of Articular Chondrocytes Independent of Cyclooxygenase Activity. J. Biol. Chem. 278: 15319-15325 [Abstract] [Full Text]  
  • Callejas, N. A., Fernandez-Martinez, A., Castrillo, A., Bosca, L., Martin-Sanz, P. (2003). Selective Inhibitors of Cyclooxygenase-2 Delay the Activation of Nuclear Factor kappa B and Attenuate the Expression of Inflammatory Genes in Murine Macrophages Treated with Lipopolysaccharide. Mol. Pharmacol. 63: 671-677 [Abstract] [Full Text]  
  • Von der Thusen, J. H., Kuiper, J., Van Berkel, T. J. C., Biessen, E. A. L. (2003). Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential. Pharmacol. Rev. 55: 133-166 [Abstract] [Full Text]  
  • Zhou, H.-R., Islam, Z., Pestka, J. J. (2003). Rapid, Sequential Activation of Mitogen-Activated Protein Kinases and Transcription Factors Precedes Proinflammatory Cytokine mRNA Expression in Spleens of Mice Exposed to the Trichothecene Vomitoxin. Toxicol Sci 72: 130-142 [Abstract] [Full Text]  
  • Wu, D., Cederbaum, A. I. (2003). Role of p38 MAPK in CYP2E1-dependent Arachidonic Acid Toxicity. J. Biol. Chem. 278: 1115-1124 [Abstract] [Full Text]  
  • Kontoyiannis, D., Boulougouris, G., Manoloukos, M., Armaka, M., Apostolaki, M., Pizarro, T., Kotlyarov, A., Forster, I., Flavell, R., Gaestel, M., Tsichlis, P., Cominelli, F., Kollias, G. (2002). Genetic Dissection of the Cellular Pathways and Signaling Mechanisms in Modeled Tumor Necrosis Factor-induced Crohn's-like Inflammatory Bowel Disease. JEM 196: 1563-1574 [Abstract] [Full Text]  
  • Chen, C.-J., Raung, S.-L., Kuo, M.-D., Wang, Y.-M. (2002). Suppression of Japanese encephalitis virus infection by non-steroidal anti-inflammatory drugs. J. Gen. Virol. 83: 1897-1905 [Abstract] [Full Text]  
  • Thun, M. J., Henley, S. J., Patrono, C. (2002). Nonsteroidal Anti-inflammatory Drugs as Anticancer Agents: Mechanistic, Pharmacologic, and Clinical Issues. JNCI J Natl Cancer Inst 94: 252-266 [Abstract] [Full Text]  
  • Perez-G., M., Melo, M., Keegan, A. D., Zamorano, J. (2002). Aspirin and Salicylates Inhibit the IL-4- and IL-13-Induced Activation of STAT6. J. Immunol. 168: 1428-1434 [Abstract] [Full Text]  
  • Zugasti, O., Rul, W., Roux, P., Peyssonnaux, C., Eychene, A., Franke, T. F., Fort, P., Hibner, U. (2001). Raf-MEK-Erk Cascade in Anoikis Is Controlled by Rac1 and Cdc42 via Akt. Mol. Cell. Biol. 21: 6706-6717 [Abstract] [Full Text]  
  • TEGEDER, I., PFEILSCHIFTER, J., GEISSLINGER, G. (2001). Cyclooxygenase-independent actions of cyclooxygenase inhibitors. FASEB J. 15: 2057-2072 [Abstract] [Full Text]  
  • Liao, C.-L., Lin, Y.-L., Wu, B.-C., Tsao, C.-H., Wang, M.-C., Liu, C.-I, Huang, Y.-L., Chen, J.-H., Wang, J.-P., Chen, L.-K. (2001). Salicylates Inhibit Flavivirus Replication Independently of Blocking Nuclear Factor Kappa B Activation. J. Virol. 75: 7828-7839 [Abstract] [Full Text]  
  • Detmer, K., Wang, Z., Warejcka, D., Leeper-Woodford, S. K., Newman, W. H. (2001). Endotoxin stimulated cytokine production in rat vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 281: H661-H668 [Abstract] [Full Text]  
  • Blandin, V., Vigne, P., Breittmayer, J. P., Frelin, C. (2001). Allosteric Inhibition of Endothelin ETA Receptors by 3,5-Dibromosalicylic Acid. Mol. Pharmacol. 58: 1461-1469 [Abstract] [Full Text]  
  • Desreumaux, P., Dubuquoy, L., Nutten, S., Peuchmaur, M., Englaro, W., Schoonjans, K., Derijard, B., Desvergne, B., Wahli, W., Chambon, P., Leibowitz, M. D., Colombel, J.-F., Auwerx, J. (2001). Attenuation of Colon Inflammation through Activators of the Retinoid X Receptor (Rxr)/Peroxisome Proliferator-Activated Receptor {gamma} (Ppar{gamma}) Heterodimer: A Basis for New Therapeutic Strategies. JEM 193: 827-838 [Abstract] [Full Text]  
  • Murphy, G. A., Jillian, S. A., Michaelson, D., Philips, M. R., D’Eustachio, P., Rush, M. G. (2001). Signaling Mediated by the Closely Related Mammalian Rho Family GTPases TC10 and Cdc42 Suggests Distinct Functional Pathways. Cell Growth Differ. 12: 157-167 [Abstract] [Full Text]  
  • van den Blink, B., Juffermans, N. P., ten Hove, T., Schultz, M. J., van Deventer, S. J. H., van der Poll, T., Peppelenbosch, M. P. (2001). p38 Mitogen-Activated Protein Kinase Inhibition Increases Cytokine Release by Macrophages In Vitro and During Infection In Vivo. J. Immunol. 166: 582-587 [Abstract] [Full Text]  
  • Bowie, A. G., O'Neill, L. A. J. (2000). Vitamin C Inhibits NF-{kappa}B Activation by TNF Via the Activation of p38 Mitogen-Activated Protein Kinase. J. Immunol. 165: 7180-7188 [Abstract] [Full Text]  
  • Alpert, D., Vilcek, J. (2000). Inhibition of Ikappa B Kinase Activity by Sodium Salicylate in Vitro Does Not Reflect Its Inhibitory Mechanism in Intact Cells. J. Biol. Chem. 275: 10925-10929 [Abstract] [Full Text]  
  • Talbodec, A., Berkane, N., Blandin, V., Breittmayer, J. P., Ferrari, E., Frelin, C., Vigne, P. (2000). Aspirin and Sodium Salicylate Inhibit Endothelin ETA Receptors by an Allosteric Type of Mechanism. Mol. Pharmacol. 57: 797-804 [Abstract] [Full Text]  
  • Engelman, J. A., Berg, A. H., Lewis, R. Y., Lin, A., Lisanti, M. P., Scherer, P. E. (1999). Constitutively Active Mitogen-activated Protein Kinase Kinase 6 (MKK6) or Salicylate Induces Spontaneous 3T3-L1 Adipogenesis. J. Biol. Chem. 274: 35630-35638 [Abstract] [Full Text]  
  • Wang, Z., Brecher, P. (1999). Salicylate Inhibition of Extracellular Signal-Regulated Kinases and Inducible Nitric Oxide Synthase. Hypertension 34: 1259-1264 [Abstract] [Full Text]  
  • Gupta, A., Rosenberger, S. F., Bowden, G. T. (1999). Increased ROS levels contribute to elevated transcription factor and MAP kinase activities in malignantly progressed mouse keratinocyte cell lines. Carcinogenesis 20: 2063-2073 [Abstract] [Full Text]  
  • Shiff, S. J., Rigas, B. (1999). The Role of Cyclooxygenase Inhibition in the Antineoplastic Effects of Nonsteroidal Antiinflammatory Drugs (Nsaids). JEM 190: 445-450 [Full Text]  
  • Alpert, D., Schwenger, P., Han, J. (1999). Cell Stress and MKK6b-mediated p38 MAP Kinase Activation Inhibit Tumor Necrosis Factor-induced Ikappa B Phosphorylation and NF-kappa B Activation. J. Biol. Chem. 274: 22176-22183 [Abstract] [Full Text]  
  • Lemay, S., Lebedeva, T. V., Singh, A. K. (1999). Inhibition of Cytokine Gene Expression by Sodium Salicylate in a Macrophage Cell Line through an NF-kappa B-Independent Mechanism. CVI 6: 567-572 [Abstract] [Full Text]  
  • Eliopoulos, A. G., Gallagher, N. J., Blake, S. M. S., Dawson, C. W., Young, L. S. (1999). Activation of the p38 Mitogen-activated Protein Kinase Pathway by Epstein-Barr Virus-encoded Latent Membrane Protein 1 Coregulates Interleukin-6 and Interleukin-8 Production. J. Biol. Chem. 274: 16085-16096 [Abstract] [Full Text]  
  • Liu, R. Y., Fan, C., Olashaw, N. E., Wang, X., Zuckerman, K. S. (1999). Tumor Necrosis Factor-alpha -induced Proliferation of Human Mo7e Leukemic Cells Occurs via Activation of Nuclear Factor kappa B Transcription Factor. J. Biol. Chem. 274: 13877-13885 [Abstract] [Full Text]  
  • Madge, L. A., Sierra-Honigmann, M. R., Pober, J. S. (1999). Apoptosis-inducing Agents Cause Rapid Shedding of Tumor Necrosis Factor Receptor 1 (TNFR1). A NONPHARMACOLOGICAL EXPLANATION FOR INHIBITION OF TNF-MEDIATED ACTIVATION. J. Biol. Chem. 274: 13643-13649 [Abstract] [Full Text]  
  • SCHREIBER;, S (1999). Activation of nuclear factor kappa B as a target for anti- inflammatory therapy. Gut 44: 309-310 [Full Text]  
  • Manna, S. K., Aggarwal, B. B. (1999). Lipopolysaccharide Inhibits TNF-Induced Apoptosis: Role of Nuclear Factor-{kappa}B Activation and Reactive Oxygen Intermediates. J. Immunol. 162: 1510-1518 [Abstract] [Full Text]  
  • SCHMID, R M, ADLER, G, LIPTAY, S, SCHREIBER, S, NIKOLAUS, S, HAMPE, J (1998). Activation of NFkappa B in inflammatory bowel disease • Reply. Gut 43: 586c-586 [Full Text]  
  • Du, M., Sansores-Garcia, L., Zu, Z., Wu, K. K.-y. (1998). Cloning and Expression Analysis of a Novel Salicylate Suppressible Gene, Hs-CUL-3, a Member of Cullin/Cdc53 Family. J. Biol. Chem. 273: 24289-24292 [Abstract] [Full Text]  
  • Matsumoto, M., Sudo, T., Saito, T., Osada, H., Tsujimoto, M. (2000). Involvement of p38 Mitogen-activated Protein Kinase Signaling Pathway in Osteoclastogenesis Mediated by Receptor Activator of NF-kappa B Ligand (RANKL). J. Biol. Chem. 275: 31155-31161 [Abstract] [Full Text]  
  • Paik, J. H., Ju, J. H., Lee, J. Y., Boudreau, M. D., Hwang, D. H. (2000). Two Opposing Effects of Non-steroidal Anti-inflammatory Drugs on the Expression of the Inducible Cyclooxygenase. MEDIATION THROUGH DIFFERENT SIGNALING PATHWAYS. J. Biol. Chem. 275: 28173-28179 [Abstract] [Full Text]  
  • Poppers, D. M., Schwenger, P., Vilcek, J. (2000). Persistent Tumor Necrosis Factor Signaling in Normal Human Fibroblasts Prevents the Complete Resynthesis of Ikappa B-alpha. J. Biol. Chem. 275: 29587-29593 [Abstract] [Full Text]  
  • Law, B. K., Waltner-Law, M. E., Entingh, A. J., Chytil, A., Aakre, M. E., Norgaard, P., Moses, H. L. (2000). Salicylate-induced Growth Arrest Is Associated with Inhibition of p70s6k and Down-regulation of c-Myc, Cyclin D1, Cyclin A, and Proliferating Cell Nuclear Antigen. J. Biol. Chem. 275: 38261-38267 [Abstract] [Full Text]  
  • Silva, A. M., Reis, L. F. L. (2000). Sodium Salicylate Induces the Expression of the Immunophilin FKBP51 and Biglycan Genes and Inhibits p34cdc2 mRNA Both in Vitro and in Vivo. J. Biol. Chem. 275: 36388-36393 [Abstract] [Full Text]  
  • Saunders, M. A., Sansores-Garcia, L., Gilroy, D. W., Wu, K. K. (2001). Selective Suppression of CCAAT/Enhancer-binding Protein beta Binding and Cyclooxygenase-2 Promoter Activity by Sodium Salicylate in Quiescent Human Fibroblasts. J. Biol. Chem. 276: 18897-18904 [Abstract] [Full Text]  
  • Lee, J. Y., Sohn, K. H., Rhee, S. H., Hwang, D. (2001). Saturated Fatty Acids, but Not Unsaturated Fatty Acids, Induce the Expression of Cyclooxygenase-2 Mediated through Toll-like Receptor 4. J. Biol. Chem. 276: 16683-16689 [Abstract] [Full Text]  
  • Spiegelman, V. S., Stavropoulos, P., Latres, E., Pagano, M., Ronai, Z.'e., Slaga, T. J., Fuchs, S. Y. (2001). Induction of beta -Transducin Repeat-containing Protein by JNK Signaling and Its Role in the Activation of NF-kappa B. J. Biol. Chem. 276: 27152-27158 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»