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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4790-4797. Prepublished online as a Blood First Edition Paper on March 2, 2006; DOI 10.1182/blood-2005-07-3058. This Article Full Text (PDF) All Versions of this Article: 2005-07-3058v1 107/12/4790    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 Sauer, I. Articles by Kovarik, P. Search for Related Content PubMed PubMed Citation Articles by Sauer, I. Articles by Kovarik, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 29, 2005 Accepted February 2, 2006 Interferons limit inflammatory responses by induction of tristetraprolin Ines Sauer, Barbara Schaljo, Claus Vogl, Irene Gattermeier, Thomas Kolbe, Mathias Muller, Perry J Blackshear, and Pavel Kovarik* Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria Institute of Animal Breeding and Genetics, Vienna University of Veterinary Medicine, Vienna, Austria Austrian Center of Biomodelling and Transgenetics, Vienna University of Veterinary Medicine, Vienna, Austria; Department of Agrobiotechnology, IFA-Tulln, University of Natural Resources and Applied Life Sciences, Vienna, Austria Austrian Center of Biomodelling and Transgenetics, Vienna University of Veterinary Medicine, Vienna, Austria; Institute of Animal Breeding and Genetics, Vienna University of Veterinary Medicine, Vienna, Austria; Department of Agrobiotechnology, IFA-Tulln, University of Natural Resources and Applied Life Sciences, Vienna, Austria Laboratory of Neurobiology, National Institute of Environmental Health Science, Research Triangle Park, North Carolina, USA * Corresponding author; email: pavel.kovarik{at}univie.ac.at. Interferons (IFNs) are cytokines with pronounced proinflammatory properties. Here we provide evidence that IFNs play a key role also in decline of inflammation by inducing expression of tristetraprolin (TTP). TTP is an RNA-binding protein that destabilizes several AU-rich element-containing mRNAs including TNF. By promoting mRNA decay TTP significantly contributes to cytokine homeostasis. Now we report that IFNs strongly stimulate expression of TTP if a co-stimulatory stress signal is provided. IFN-induced expression of TTP depends on the IFN-activated transcription factor STAT1, and the co-stimulatory stress signal requires p38 MAPK. Within the TTP promoter we have identified a functional gamma interferon-activated sequence that recruits STAT1. Consistently, STAT1 is required for full expression of TTP in response to LPS that stimulates both p38 MAPK and, indirectly, interferon signaling. We demonstrate that in macrophages IFN-induced TTP protein limits LPS-stimulated expression of several proinflammatory genes such as TNF, IL-6, Ccl2 and Ccl3. Thus, our findings establish a link between interferon responses and TTP-mediated mRNA decay during inflammation, and propose a novel immunomodulatory role of IFNs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. M. Schichl, U. Resch, R. Hofer-Warbinek, and R. de Martin Tristetraprolin Impairs NF-{kappa}B/p65 Nuclear Translocation J. Biol. Chem., October 23, 2009; 284(43): 29571 - 29581. [Abstract] [Full Text] [PDF] B. Schaljo, F. Kratochvill, N. Gratz, I. Sadzak, I. Sauer, M. Hammer, C. Vogl, B. Strobl, M. Muller, P. J. Blackshear, et al. Tristetraprolin Is Required for Full Anti-Inflammatory Response of Murine Macrophages to IL-10 J. Immunol., July 15, 2009; 183(2): 1197 - 1206. [Abstract] [Full Text] [PDF] R. L. Ogilvie, J. R. SternJohn, B. Rattenbacher, I. A. Vlasova, D. A. Williams, H. H. Hau, P. J. Blackshear, and P. R. Bohjanen Tristetraprolin Mediates Interferon-{gamma} mRNA Decay J. Biol. Chem., April 24, 2009; 284(17): 11216 - 11223. [Abstract] [Full Text] [PDF] P.-H. Park, H. Huang, M. R. McMullen, P. Mandal, L. Sun, and L. E. Nagy Suppression of Lipopolysaccharide-stimulated Tumor Necrosis Factor-{alpha} Production by Adiponectin Is Mediated by Transcriptional and Post-transcriptional Mechanisms J. Biol. Chem., October 3, 2008; 283(40): 26850 - 26858. [Abstract] [Full Text] [PDF] U. Jalonen, E.-L. Paukkeri, and E. Moilanen Compounds That Increase or Mimic Cyclic Adenosine Monophosphate Enhance Tristetraprolin Degradation in Lipopolysaccharide-Treated Murine J774 Macrophages J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 514 - 522. [Abstract] [Full Text] [PDF] J. Emmons, W.H. D. Townley-Tilson, K. M. Deleault, S. J. Skinner, R. H. Gross, M. L. Whitfield, and S. A. Brooks Identification of TTP mRNA targets in human dendritic cells reveals TTP as a critical regulator of dendritic cell maturation RNA, May 1, 2008; 14(5): 888 - 902. [Abstract] [Full Text] [PDF] H. Cao, J. F. Urban Jr, and R. A. Anderson Cinnamon Polyphenol Extract Affects Immune Responses by Regulating Anti- and Proinflammatory and Glucose Transporter Gene Expression in Mouse Macrophages J. Nutr., May 1, 2008; 138(5): 833 - 840. [Abstract] [Full Text] [PDF] S. Datta, R. Biswas, M. Novotny, P. G. Pavicic Jr., T. Herjan, P. Mandal, and T. A. Hamilton Tristetraprolin Regulates CXCL1 (KC) mRNA Stability J. Immunol., February 15, 2008; 180(4): 2545 - 2552. [Abstract] [Full Text] [PDF] E. N. Benveniste and H. Qin Type I Interferons as Anti-Inflammatory Mediators Sci. Signal., December 11, 2007; 2007(416): pe70 - pe70. [Abstract] [Full Text] [PDF] K. S. A. Khabar Rapid transit in the immune cells: the role of mRNA turnover regulation J. Leukoc. Biol., June 1, 2007; 81(6): 1335 - 1344. 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