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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4351-4358. Prepublished online as a Blood First Edition Paper on August 23, 2005; DOI 10.1182/blood-2005-03-1029. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: 2005-03-1029v1 106/13/4351    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 Helming, L. Articles by Lengeling, A. Search for Related Content PubMed PubMed Citation Articles by Helming, L. Articles by Lengeling, A. Related Collections Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES 1,25-dihydroxyvitamin D3 is a potent suppressor of interferon –mediated macrophage activation Laura Helming, Jens Böse, Jan Ehrchen, Stefanie Schiebe, Thomas Frahm, Robert Geffers, Michael Probst-Kepper, Rudi Balling, and Andreas Lengeling From the Junior Research Group Infection Genetics, German Research Centre for Biotechnology, Braunschweig, Germany; Institute for Experimental Dermatology, University of Münster, Münster, Germany; Department of Gene Regulation and Differentiation, German Research Centre for Biotechnology, Braunschweig, Germany; Research Group Mucosal Immunity, German Research Centre for Biotechnology, Braunschweig, Germany; German Research Centre for Biotechnology, Braunschweig, Germany; and Department of Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the activated vitamin D3 hormone, is a key regulator of calcium homeostasis and thereby indispensable for bone metabolism. In addition, 1,25(OH)2D3 is known to mediate predominantly immunosuppressive responses in vitro and in vivo. It has been demonstrated that macrophages can produce 1,25(OH)2D3 on activation with interferon (IFN-), although little is understood about the biologic significance of this response. We show here that 1,25(OH)2D3 can selectively suppress key effector functions of IFN-–activated macrophages. Among these are the suppression of listericidal activity, the inhibition of phagocyte oxidase-mediated oxidative burst, and the suppression of important IFN-–induced genes, including Ccl5, Cxcl10, Cxcl9, Irf2, Fcgr1, Fcgr3, and Tlr2. The deactivation of IFN-–stimulated macrophages is dependent on a functional vitamin D receptor and 1,25(OH)2D3 acts specifically on IFN-–activated macrophages, whereas the steroid has no effects on resting macrophages. Therefore, the 1,25(OH)2D3–mediated suppression of macrophage functions is distinct from previously described macrophage deactivation mechanisms. In conclusion, our data indicate that the production of 1,25(OH)2D3 by IFN-–stimulated macrophages might be an important negative feedback mechanism to control innate and inflammatory responses of activated macrophages. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Agarwal Vitamin D, Proteinuria, Diabetic Nephropathy, and Progression of CKD Clin. J. Am. Soc. Nephrol., September 1, 2009; 4(9): 1523 - 1528. [Abstract] [Full Text] [PDF] D. Bruce, J. P. Whitcomb, A. August, M. A. McDowell, and M. T. Cantorna Elevated non-specific immunity and normal Listeria clearance in young and old vitamin D receptor knockout mice Int. Immunol., February 1, 2009; 21(2): 113 - 122. [Abstract] [Full Text] [PDF] R. Bouillon, G. Carmeliet, L. Verlinden, E. van Etten, A. 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