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 Castrillo, A.
Right arrow Articles by Boscá, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Castrillo, A.
Right arrow Articles by Boscá, L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2003, p. 1196-1208, Vol. 23, No. 4
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.4.1196-1208.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Potentiation of Protein Kinase C {zeta} Activity by 15-Deoxy-{Delta}12,14-Prostaglandin J2 Induces an Imbalance between Mitogen-Activated Protein Kinases and NF-{kappa}B That Promotes Apoptosis in Macrophages

Antonio Castrillo,1,{dagger} Paqui G. Través,1 Paloma Martín-Sanz,1 Scott Parkinson,2 Peter J. Parker,2 and Lisardo Boscá1*

Instituto de Bioquímica (Centro Mixto CSIC-UCM), Facultad de Farmacia, and Centro Nacional de Investigaciones Cardiovasculares, 28040 Madrid, Spain,1 Protein Phosphorylation Laboratory, Cancer Research UK Lincoln's Inn Fields Laboratories, London WC2A 3PX, United Kingdom2

Received 8 May 2002/ Returned for modification 4 June 2002/ Accepted 21 November 2002

Activation of the macrophage cell line RAW 264.7 with lipopolysaccharide (LPS) transiently activates protein kinase C {zeta} (PKC{zeta}) and Jun N-terminal kinase (JNK) through a phosphoinositide-3-kinase (PI3-kinase)-dependent pathway. Incubation of LPS-treated cells with the cyclopentenone 15-deoxy-{Delta}12,14-prostaglandin J2 (15dPGJ2) promoted a sustained activation of PKC{zeta} and JNK and inhibited I{kappa}B kinase (IKK) and NF-{kappa}B activity. Accordingly, 15dPGJ2 induced an imbalance between JNK and IKK activities by increasing the former signaling pathway and inhibiting the latter signaling pathway. Under these conditions, apoptosis was significantly enhanced; this response was very dependent on PKC{zeta} and JNK activation. The effect of 15dPGJ2 on PKC{zeta} activity observed in LPS-activated macrophages was not dependent on a direct action of this prostaglandin on the enzyme but was due to the activation of a step upstream of PI3-kinase. Moreover, LPS promoted the redistribution of activated PKC{zeta} from the cytosol to the nucleus, a process that was enhanced by treatment of the cells with 15dPGJ2 that favored a persistent and broader distribution of PKC{zeta} in the nucleus. These results indicate that 15dPGJ2 and other cyclopentenone prostaglandins, through the sustained activation of PKC{zeta}, might contribute significantly to the process of resolution of inflammation by promoting apoptosis of activated macrophages.

* Corresponding author. Mailing address: Instituto de Bioquímica, Facultad de Farmacia, 28040 Madrid, Spain. Phone: 3491 3941853. Fax: 3491 543 8649. E-mail: boscal{at}farm.ucm.es.

{dagger} Present address: Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095-1662.

Molecular and Cellular Biology, February 2003, p. 1196-1208, Vol. 23, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.4.1196-1208.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Paranjpe, A., Cacalano, N. A., Hume, W. R., Jewett, A. (2009). N-Acetyl Cysteine Mediates Protection from 2-Hydroxyethyl Methacrylate Induced Apoptosis via Nuclear Factor Kappa B-Dependent and Independent Pathways: Potential Involvement of JNK. Toxicol Sci 108: 356-366 [Abstract] [Full Text]  
  • Haworth, O., Buckley, C. D. (2007). Resolving the problem of persistence in the switch from acute to chronic inflammation. Proc. Natl. Acad. Sci. USA 104: 20647-20648 [Full Text]  
  • Moulakakis, C., Adam, S., Seitzer, U., Schromm, A. B., Leitges, M., Stamme, C. (2007). Surfactant Protein A Activation of Atypical Protein Kinase C {zeta} in I{kappa}B-{alpha}-Dependent Anti-Inflammatory Immune Regulation. J. Immunol. 179: 4480-4491 [Abstract] [Full Text]  
  • Garin, G., Abe, J.-i., Mohan, A., Lu, W., Yan, C., Newby, A. C., Rhaman, A., Berk, B. C. (2007). Flow Antagonizes TNF-{alpha} Signaling in Endothelial Cells by Inhibiting Caspase-Dependent PKC{zeta} Processing. Circ. Res. 101: 97-105 [Abstract] [Full Text]  
  • Sandig, H., Pease, J. E., Sabroe, I. (2007). Contrary prostaglandins: the opposing roles of PGD2 and its metabolites in leukocyte function. J. Leukoc. Biol. 81: 372-382 [Abstract] [Full Text]  
  • Alfranca, A., Iniguez, M. A., Fresno, M., Redondo, J. M. (2006). Prostanoid signal transduction and gene expression in the endothelium: Role in cardiovascular diseases. Cardiovasc Res 70: 446-456 [Abstract] [Full Text]  
  • Monsalve, E., Perez, M. A., Rubio, A., Ruiz-Hidalgo, M. J., Baladron, V., Garcia-Ramirez, J. J., Gomez, J. C., Laborda, J., Diaz-Guerra, M. J. M. (2006). Notch-1 Up-Regulation and Signaling following Macrophage Activation Modulates Gene Expression Patterns Known to Affect Antigen-Presenting Capacity and Cytotoxic Activity. J. Immunol. 176: 5362-5373 [Abstract] [Full Text]  
  • Wu, W., Mosteller, R. D., Broek, D. (2004). Sphingosine Kinase Protects Lipopolysaccharide-Activated Macrophages from Apoptosis. Mol. Cell. Biol. 24: 7359-7369 [Abstract] [Full Text]  
  • Grau, R., Iniguez, M. A., Fresno, M. (2004). Inhibition of Activator Protein 1 Activation, Vascular Endothelial Growth Factor, and Cyclooxygenase-2 Expression by 15-Deoxy-{Delta}12,14-Prostaglandin J2 in Colon Carcinoma Cells: Evidence for a Redox-Sensitive Peroxisome Proliferator-Activated Receptor-{gamma}-Independent Mechanism. Cancer Res. 64: 5162-5171 [Abstract] [Full Text]  
  • Teusch, N., Lombardo, E., Eddleston, J., Knaus, U. G. (2004). The Low Molecular Weight GTPase RhoA and Atypical Protein Kinase C{zeta} Are Required for TLR2-Mediated Gene Transcription. J. Immunol. 173: 507-514 [Abstract] [Full Text]  
  • Zhang, Y., Chen, F. (2004). Reactive Oxygen Species (ROS), Troublemakers between Nuclear Factor-{kappa}B (NF-{kappa}B) and c-Jun NH2-terminal Kinase (JNK). Cancer Res. 64: 1902-1905 [Abstract] [Full Text]  
  • Uhlig, U., Fehrenbach, H., Lachmann, R. A., Goldmann, T., Lachmann, B., Vollmer, E., Uhlig, S. (2004). Phosphoinositide 3-OH Kinase Inhibition Prevents Ventilation-induced Lung Cell Activation. Am. J. Respir. Crit. Care Med. 169: 201-208 [Abstract] [Full Text]  
  • Perez-Sala, D., Cernuda-Morollon, E., Canada, F. J. (2003). Molecular Basis for the Direct Inhibition of AP-1 DNA Binding by 15-Deoxy-{Delta}12,14-prostaglandin J2. J. Biol. Chem. 278: 51251-51260 [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»