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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 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 Citation Map 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. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Interferons limit inflammatory responses by induction of tristetraprolin Ines Sauer, Barbara Schaljo, Claus Vogl, Irene Gattermeier, Thomas Kolbe, Mathias Müller, Perry J. Blackshear, and Pavel Kovarik From the Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna; the Austrian Center of Biomodelling and Transgenetics and the Institute of Animal Breeding and Genetics, Vienna University of Veterinary Medicine; the Department of Agrobiotechnology, IFA (Interuniversity Research Center)–Tulln, University of Natural Resources and Applied Life Sciences, Vienna, Austria; and the Laboratory of Neurobiology, National Institute of Environmental Health Science, Research Triangle Park, NC. Interferons (IFNs) are cytokines with pronounced proinflammatory properties. Here we provide evidence that IFNs also play a key role in decline of inflammation by inducing expression of tristetraprolin (Ttp). TTP is an RNA-binding protein that destabilizes several AU-rich elementcontaining 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 costimulatory stress signal is provided. IFN-induced expression of Ttp depends on the IFNactivated transcription factor STAT1, and the costimulatory 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: 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. [Abstract] [Full Text] [PDF]

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