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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-12-3771. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3771v1 102/4/1178    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 Dai, Y. Articles by Hamilton, T. A. Search for Related Content PubMed PubMed Citation Articles by Dai, Y. Articles by Hamilton, T. A. Related Collections Immunobiology Signal Transduction Gene Expression Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 August 2003, Vol. 102, No. 4, pp. 1178-1185 CHEMOKINES TGF inhibits LPS-induced chemokine mRNA stabilization Yalei Dai, Shyamsree Datta, Michael Novotny, and Thomas A. Hamilton From the Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH. The mechanisms involved in anti-inflammatory action of transforming growth factor (TGF) have been examined by evaluating its effect on chemokine gene expression in mouse macrophages. Lipopolysaccharide (LPS)–stimulated expression of the CXC chemokines KC and MIP-2 was selectively reduced by TGF in a time- and protein synthesis–dependent process. While TGF had a modest effect on transcription of the KC and MIP-2 mRNAs as measured by nuclear run-on, it had no effect on LPS-stimulated luciferase expression driven by the KC promoter nor on the activation of nuclear factor B (NFB) DNA-binding activity and transactivation function. Interestingly, KC mRNA levels were markedly reduced by TGF treatment in cells transfected with KC genomic or cDNA constructs driven from either the KC or cytomegalovirus (CMV) promoters, demonstrating the importance of sequences within the mature mRNA and suggesting that suppression may involve a posttranscriptional mechanism. In support of this possibility, LPS stimulation prolonged the half-life of KC mRNA and this stabilization response was blocked in cells treated with TGF. Examination of KC mRNA expressed under control of a tetracycline-responsive promoter demonstrated that TGF prevented stabilization of KC mRNA, in response to LPS but did not alter KC mRNA half-life directly. KC mRNA stabilization by LPS was dependent on activation of p38 mitogen-activated protein kinase (MAPK) activity, and TGF treatment inhibited p38 MAPK activation. These findings support the hypothesis that TGF-mediated suppression of chemokine gene expression involves antagonism of LPS-stimulated KC mRNA stabilization via inhibition of p38 MAPK. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. C. Flanders, B. M. Ho, P. R. Arany, C. Stuelten, M. Mamura, M. O. Paterniti, A. Sowers, J. B. Mitchell, and A. B. Roberts Absence of Smad3 Induces Neutrophil Migration after Cutaneous Irradiation: Possible Contribution to Subsequent Radioprotection Am. J. Pathol., July 1, 2008; 173(1): 68 - 76. [Abstract] [Full Text] [PDF] J. Hartupee, X. Li, and T. Hamilton Interleukin 1{alpha}-induced NF{kappa}B Activation and Chemokine mRNA Stabilization Diverge at IRAK1 J. Biol. Chem., June 6, 2008; 283(23): 15689 - 15693. [Abstract] [Full Text] [PDF] J. Hartupee, C. Liu, M. Novotny, X. Li, and T. Hamilton IL-17 Enhances Chemokine Gene Expression through mRNA Stabilization J. Immunol., September 15, 2007; 179(6): 4135 - 4141. [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] A. Bobik Transforming Growth Factor-{beta}s and Vascular Disorders Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1712 - 1720. [Abstract] [Full Text] [PDF]

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