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Blood, 1 January 2005, Vol. 105, No. 1, pp. 282-288. Prepublished online as a Blood First Edition Paper on September 2, 2004; DOI 10.1182/blood-2004-07-2782. This Article Full Text (PDF) All Versions of this Article: 2004-07-2782v1 105/1/282    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mavropoulos, A. Articles by Clark, A. R Search for Related Content PubMed PubMed Citation Articles by Mavropoulos, A. Articles by Clark, A. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 21, 2004 Accepted August 22, 2004 Stabilization of IFN- mRNA by MAPK p38 in IL-12- and IL-18-stimulated human NK cells Athanasios Mavropoulos, Gareth Sully, Andrew P Cope, and Andrew R Clark* Kennedy Institute of Rheumatology Division, Imperial College London, London, United Kingdom * Corresponding author; email: andy.clark{at}imperial.ac.uk. The rapid induction of IFN- by innate cytokines such as IL-12 and IL-18 is critical for immunity against infectious pathogens. We investigated the molecular mechanisms underlying this response. IL-12 and IL-18 rapidly and synergistically induced the secretion of IFN- by freshly purified human peripheral blood lymphocytes. At early time points IFN- was expressed almost exclusively by natural killer cells, and in both CD56bright and CD56dim sub-populations. Mitogen activated protein kinase p38 was activated strongly by IL-18 and weakly by IL-12 in natural killer cells, but was not activated by either cytokine in T cells. The expression of IFN- mRNA and protein was dose-dependently blocked by SB203580, a specific inhibitor of mitogen activated protein kinase p38, which also caused a dramatic destabilization of IFN- mRNA. The 3' untranslated region of IFN- mRNA conferred p38-responsiveness to a heterologous reporter mRNA. Therefore the synergistic induction of IFN- by IL-12 and IL-18 in natural killer cells is mediated at least in part by p38-dependent and 3' UTR-mediated stabilization of IFN- mRNA. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Gross, C. Grupp, C. Steinberg, S. Zimmermann, D. Strasser, N. Hannesschlager, W. Reindl, H. Jonsson, H. Huo, D. R. Littman, et al. Multiple ITAM-coupled NK-cell receptors engage the Bcl10/Malt1 complex via Carma1 for NF-{kappa}B and MAPK activation to selectively control cytokine production Blood, September 15, 2008; 112(6): 2421 - 2428. [Abstract] [Full Text] [PDF] V. Athie-Morales, G. M. O'Connor, and C. M. Gardiner Activation of Human NK Cells by the Bacterial Pathogen-Associated Molecular Pattern Muramyl Dipeptide J. Immunol., March 15, 2008; 180(6): 4082 - 4089. [Abstract] [Full Text] [PDF] P. Schierloh, N. Yokobori, M. Aleman, V. Landoni, L. Geffner, R. M. Musella, J. Castagnino, M. Baldini, E. Abbate, S. S. de la Barrera, et al. Mycobacterium tuberculosis-Induced Gamma Interferon Production by Natural Killer Cells Requires Cross Talk with Antigen-Presenting Cells Involving Toll-Like Receptors 2 and 4 and the Mannose Receptor in Tuberculous Pleurisy Infect. Immun., November 1, 2007; 75(11): 5325 - 5337. [Abstract] [Full Text] [PDF] S. M. Abraham, T. Lawrence, A. Kleiman, P. Warden, M. Medghalchi, J. Tuckermann, J. Saklatvala, and A. R. Clark Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1 J. Exp. Med., August 7, 2006; 203(8): 1883 - 1889. [Abstract] [Full Text] [PDF] L. S. Berenson, J. Yang, B. P. Sleckman, T. L. Murphy, and K. M. Murphy Selective Requirement of p38{alpha} MAPK in Cytokine-Dependent, but Not Antigen Receptor-Dependent, Th1 Responses. J. Immunol., April 15, 2006; 176(8): 4616 - 4621. [Abstract] [Full Text] [PDF] J. P. Luyendyk, L. D. Lehman-McKeeman, D. M. Nelson, V. M. Bhaskaran, T. P. Reilly, B. D. Car, G. H. Cantor, J. F. Maddox, P. E. Ganey, and R. A. Roth Unique Gene Expression and Hepatocellular Injury in the Lipopolysaccharide-Ranitidine Drug Idiosyncrasy Rat Model: Comparison with Famotidine Toxicol. Sci., April 1, 2006; 90(2): 569 - 585. [Abstract] [Full Text] [PDF] J.-S. Chang, J. F. Huggett, K. Dheda, L. U. Kim, A. Zumla, and G. A. W. Rook Myobacterium tuberculosis Induces Selective Up-Regulation of TLRs in the Mononuclear Leukocytes of Patients with Active Pulmonary Tuberculosis. J. Immunol., March 1, 2006; 176(5): 3010 - 3018. [Abstract] [Full Text] [PDF]

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