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Peroxisome proliferator-activated receptor-gamma and its ligands attenuate biologic functions of human natural killer cells

  1. Author:
    Zhang, X.
    Rodriguez-Galan, M. C.
    Subleski, J. J.
    Ortaldo, J. R.
    Hodge, D. L.
    Wang, J. M.
    Shimozato, O.
    Reynolds, D. A.
    Young, H. A.

  2. Author Address

    NCI, Expt Immunol Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA Young, HA, NCI, Expt Immunol Lab, Canc Res Ctr, NIH, Bldg 560,Rm 31-23, Frederick, MD 21702 USA
    1. Year: 2004
    2. Date: NOV 15
  2. Journal: Blood
    1. 104
    2. 10
    3. Pages: 3276-3284
  4. Type of Article: Article
  1. Abstract:

    Interferon-gamma (IFN-gamma) 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-gamma (PPAR-gamma) ligands via both PPAR-gamma-dependent and -independent pathways due to variation in PPAR-gamma expression. In PPAR-gamma-null NK cells, 15-deoxy-Delta(12,14) prostaglandin J(2) (15d-PGJ(2)), a natural PPAR-gamma ligand, reduces IFN-gamma 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 PPARgamma-positive NK cells, PPAR-gamma activation by 15d-PGJ2 and ciglitazone (a synthetic ligand) leads to reduction in both mRNA and protein levels of IFN-gamma. Overexpression of PPAR-gamma in PPAR-gamma-null NK cells reduces IFN-gamma gene expression. However, PPAR-gamma expression and activation has no effect on NK cell cytolytic activity. In addition, 15d-PGJ(2) 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. (C) 2004 by The American Society of Hematology

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External Sources

  1. View record in Web of Science®
  2. WOS: 000225094100048

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