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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1158-1165. Prepublished online as a Blood First Edition Paper on February 12, 2008; DOI 10.1182/blood-2007-08-109645. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-08-109645v1 112/4/1158    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 Lawrence, B. P. Articles by Woisetschläger, M. Search for Related Content PubMed PubMed Citation Articles by Lawrence, B. P. Articles by Woisetschläger, M. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Activation of the aryl hydrocarbon receptor is essential for mediating the anti-inflammatory effects of a novel low-molecular-weight compound B. Paige Lawrence1, Michael S. Denison2, Hermann Novak3, Beth A. Vorderstrasse4, Nathalie Harrer3, Wolfgang Neruda3, Claudia Reichel3, and Maximilian Woisetschläger3 1 Department of Environmental Medicine, University of Rochester, NY; 2 Department of Environmental Toxicology, University of California–Davis, Davis; 3 Department of Autoimmunity and Transplantation, Novartis Institute for Biomedical Research, Vienna, Austria; and 4 Department of Pharmaceutical Sciences, Washington State University, Pullman VAF347 is a low-molecular-weight compound that inhibits allergic lung inflammation in vivo. This effect is likely the result of a block of dendritic cell (DC) function to generate proinflammatory T-helper (Th) cells because VAF347 inhibits interleukin (IL)–6, CD86, and human leukocyte antigen (HLA)–DR expression by human monocyte-derived DC, 3 relevant molecules for Th-cell generation. Here we demonstrate that VAF347 interacts with the aryl hydrocarbon receptor (AhR) protein, resulting in activation of the AhR signaling pathway. Functional AhR is responsible for the biologic activity of VAF347 because (1) other AhR agonists display an identical activity profile in vitro, (2) gene silencing of wild-type AhR expression or forced overexpression of a trans-dominant negative AhR ablates VAF347 activity to inhibit cytokine induced IL-6 expression in a human monocytic cell line, and (3) AhR-deficient mice are resistant to the compound's ability to block allergic lung inflammation in vivo. These data identify the AhR protein as key molecular target of VAF347 and its essential role for mediating the anti-inflammatory effects of the compound in vitro and in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Ah receptor: xenobiotic response meets inflammation Qiang Ma Blood 2008 112: 928-929. [Full Text] [PDF] This article has been cited by other articles: B. Platzer, S. Richter, D. Kneidinger, D. Waltenberger, M. Woisetschlager, and H. Strobl Aryl Hydrocarbon Receptor Activation Inhibits In Vitro Differentiation of Human Monocytes and Langerhans Dendritic Cells J. Immunol., July 1, 2009; 183(1): 66 - 74. [Abstract] [Full Text] [PDF] B. Jux, S. Kadow, and C. Esser Langerhans Cell Maturation and Contact Hypersensitivity Are Impaired in Aryl Hydrocarbon Receptor-Null Mice J. Immunol., June 1, 2009; 182(11): 6709 - 6717. [Abstract] [Full Text] [PDF] E. Hauben, S. Gregori, E. Draghici, B. Migliavacca, S. Olivieri, M. Woisetschlager, and M. G. Roncarolo Activation of the aryl hydrocarbon receptor promotes allograft-specific tolerance through direct and dendritic cell-mediated effects on regulatory T cells Blood, August 15, 2008; 112(4): 1214 - 1222. [Abstract] [Full Text] [PDF]

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