HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Varghese, J. Articles by Sarin, A. Search for Related Content PubMed PubMed Citation Articles by Varghese, J. Articles by Sarin, A.

Inhibition of p38 Kinase Reveals a TNF--Mediated, Caspase-Dependent, Apoptotic Death Pathway in a Human Myelomonocyte Cell Line¹

National Centre for Biological Sciences, Bangalore, Karnataka, India

TNF- transduces signals of survival or death via its two receptors, R1/p55/p60 and RII/p80/p75. The role of caspases as effectors of cell death is universally accepted, although caspase inhibitors may potentiate TNF cytotoxicity in some instances. In conditions when macromolecular synthesis is blocked, caspases are part of the machinery that executes TNF-triggered apoptotic death in U937, a human myelomonocyte cell line, and in the Jurkat T cell line. However, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) triggered TNF cytotoxicity in U937 cells and murine splenic macrophages, but not the Jurkat cell line. TNF induced expression of the antiapoptotic protein c-IAP2 (cytoplasmic inhibitor of apoptosis protein 2), and was blocked in the presence of a p38 MAPK inhibitor, which also induced caspase-dependent, TNF-mediated apoptosis in U937 cells. Thus, inhibition of p38 MAPK resulted in the activation of caspase 9 and cleavage of the adaptor molecule BH3 interacting domain death agonist, and blocked NF-B-mediated transactivation, without affecting the nuclear translocation of NF-B. Collectively, these data show that activation of p38 MAPK is critical to cell survival by TNF in U937 cells, and demonstrate lineage-specific regulation of TNF-triggered signals of activation or apoptosis.

This article has been cited by other articles:

				P. J. Shaw, P. E. Ganey, and R. A. Roth Tumor Necrosis Factor{alpha} Is a Proximal Mediator of Synergistic Hepatotoxicity from Trovafloxacin/Lipopolysaccharide Coexposure J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 62 - 68. [Abstract] [Full Text] [PDF]

				W. Aerbajinai, J. Zhu, Z. Gao, K. Chin, and G. P. Rodgers Thalidomide induces {gamma}-globin gene expression through increased reactive oxygen species mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis Blood, October 15, 2007; 110(8): 2864 - 2871. [Abstract] [Full Text] [PDF]

				J. Zalevsky, T. Secher, S. A. Ezhevsky, L. Janot, P. M. Steed, C. O'Brien, A. Eivazi, J. Kung, D.-H. T. Nguyen, S. K. Doberstein, et al. Dominant-Negative Inhibitors of Soluble TNF Attenuate Experimental Arthritis without Suppressing Innate Immunity to Infection J. Immunol., August 1, 2007; 179(3): 1872 - 1883. [Abstract] [Full Text] [PDF]

				J. Zhang, T. N. Bui, J. Xiang, and A. Lin Cyclic AMP Inhibits p38 Activation via CREB-Induced Dynein Light Chain Mol. Cell. Biol., February 15, 2006; 26(4): 1223 - 1234. [Abstract] [Full Text] [PDF]

				K. Ueda, H. Kosako, Y. Fukui, and S. Hattori Proteomic Identification of Bcl2-associated Athanogene 2 as a Novel MAPK-activated Protein Kinase 2 Substrate J. Biol. Chem., October 1, 2004; 279(40): 41815 - 41821. [Abstract] [Full Text] [PDF]

				H. Nishihara, M. Hwang, S. Kizaka-Kondoh, L. Eckmann, and P. A. Insel Cyclic AMP Promotes cAMP-responsive Element-binding Protein-dependent Induction of Cellular Inhibitor of Apoptosis Protein-2 and Suppresses Apoptosis of Colon Cancer Cells through ERK1/2 and p38 MAPK J. Biol. Chem., June 18, 2004; 279(25): 26176 - 26183. [Abstract] [Full Text] [PDF]

				S.-J. Kim, S.-G. Hwang, I.-C. Kim, and J.-S. Chun Actin Cytoskeletal Architecture Regulates Nitric Oxide-induced Apoptosis, Dedifferentiation, and Cyclooxygenase-2 Expression in Articular Chondrocytes via Mitogen-activated Protein Kinase and Protein Kinase C Pathways J. Biol. Chem., October 24, 2003; 278(43): 42448 - 42456. [Abstract] [Full Text] [PDF]

				J.-B. Yoon, S.-J. Kim, S.-G. Hwang, S. Chang, S.-S. Kang, and J.-S. Chun Non-steroidal Anti-inflammatory Drugs Inhibit Nitric Oxide-induced Apoptosis and Dedifferentiation of Articular Chondrocytes Independent of Cyclooxygenase Activity J. Biol. Chem., April 18, 2003; 278(17): 15319 - 15325. [Abstract] [Full Text] [PDF]

				J. C. Fanzo, C.-M. Hu, S. Y. Jang, and A. B. Pernis Regulation of Lymphocyte Apoptosis by Interferon Regulatory Factor 4 (IRF-4) J. Exp. Med., February 3, 2003; 197(3): 303 - 314. [Abstract] [Full Text] [PDF]

				H.-F. Cheng and R. C. Harris Cyclooxygenase-2 Expression in Cultured Cortical Thick Ascending Limb of Henle Increases in Response to Decreased Extracellular Ionic Content by Both Transcriptional and Post-transcriptional Mechanisms. ROLE OF p38-MEDIATED PATHWAYS J. Biol. Chem., November 15, 2002; 277(47): 45638 - 45643. [Abstract] [Full Text] [PDF]

				J. Varghese, H. Sade, P. Vandenabeele, and A. Sarin Head Involution Defective (Hid)-triggered Apoptosis Requires Caspase-8 but Not FADD (Fas-associated Death Domain) and Is Regulated by Erk in Mammalian Cells J. Biol. Chem., September 13, 2002; 277(38): 35097 - 35104. [Abstract] [Full Text] [PDF]

				S.-J. Kim, H.-G. Kim, C.-D. Oh, S.-G. Hwang, W.-K. Song, Y.-J. Yoo, S.-S. Kang, and J.-S. Chun p38 Kinase-dependent and -independent Inhibition of Protein Kinase C zeta and -alpha Regulates Nitric Oxide-induced Apoptosis and Dedifferentiation of Articular Chondrocytes J. Biol. Chem., August 9, 2002; 277(33): 30375 - 30381. [Abstract] [Full Text] [PDF]