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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3276-3284. Prepublished online as a Blood First Edition Paper on July 20, 2004; DOI 10.1182/blood-2004-02-0664. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-02-0664v1 104/10/3276    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 Zhang, X. Articles by Young, H. A. Search for Related Content PubMed PubMed Citation Articles by Zhang, X. Articles by Young, H. A. Related Collections Immunobiology Signal Transduction Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Peroxisome proliferator-activated receptor- and its ligands attenuate biologic functions of human natural killer cells Xia Zhang, Maria Cecilia Rodriguez-Galán, Jeff J. Subleski, John R. Ortaldo, Deborah L. Hodge, Ji-Ming Wang, Osamu Shimozato, Della A. Reynolds, and Howard A. Young From the Laboratory of Experimental Immunology and Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD. Interferon- (IFN-) production and cytolytic activity are 2 major biologic functions of natural killer (NK) cells that are important for innate immunity. We demonstrate here that these functions are compromised in human NK cells treated with peroxisome proliferator-activated- (PPAR-) ligands via both PPAR--dependent and -independent pathways due to variation in PPAR- expression. In PPAR--null NK cells, 15-deoxy-12,14 prostaglandin J2 (15d-PGJ2), a natural PPAR- ligand, reduces IFN- production that can be reversed by MG132 and/or chloroquine, and it inhibits cytolytic activity of NK cells through reduction of both conjugate formation and CD69 expression. In PPAR-positive NK cells, PPAR- activation by 15d-PGJ2 and ciglitazone (a synthetic ligand) leads to reduction in both mRNA and protein levels of IFN-. Overexpression of PPAR- in PPAR--null NK cells reduces IFN- gene expression. However, PPAR- expression and activation has no effect on NK cell cytolytic activity. In addition, 15d-PGJ2 but not ciglitazone reduces expression of CD69 in human NK cells, whereas CD44 expression is not affected. These results reveal novel pathways regulating NK cell biologic functions and provide a basis for the design of therapeutic agents that can regulate the function of NK cells within the innate immune response. (Blood. 2004;104:3276-3284) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The yin-yang in immunity Bo Dupont Blood 2004 104: 3002-3003. [Full Text] [PDF] This article has been cited by other articles: Y. Chen, B. Perussia, and K. S. Campbell Prostaglandin D2 Suppresses Human NK Cell Function via Signaling through D Prostanoid Receptor J. Immunol., September 1, 2007; 179(5): 2766 - 2773. [Abstract] [Full Text] [PDF] C. Fionda, F. Nappi, M. Piccoli, L. Frati, A. Santoni, and M. Cippitelli 15-Deoxy-{Delta}12,14-Prostaglandin J2 Negatively Regulates rankl Gene Expression in Activated T Lymphocytes: Role of NF-{kappa}B and Early Growth Response Transcription Factors J. Immunol., April 1, 2007; 178(7): 4039 - 4050. [Abstract] [Full Text] [PDF] H. Sandig, J. E. Pease, and I. Sabroe Contrary prostaglandins: the opposing roles of PGD2 and its metabolites in leukocyte function J. Leukoc. Biol., February 1, 2007; 81(2): 372 - 382. [Abstract] [Full Text] [PDF] B. L. F. Kaplan, Y. Ouyang, C. E. Rockwell, G. K. Rao, and N. E. Kaminski 2-Arachidonoyl-glycerol suppresses interferon-{gamma} production in phorbol ester/ionomycin-activated mouse splenocytes independent of CB1 or CB2 J. Leukoc. Biol., June 1, 2005; 77(6): 966 - 974. [Abstract] [Full Text] [PDF]

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