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Differential regulation of chemokine gene expression by 15- deoxy-Delta(12,14) prostaglandin J(2)

  1. Author:
    Zhang, X.
    Wang, J. M.
    Gong, W. H.
    Mukaida, N.
    Young, H. A.

  2. Author Address

    NCI, Frederick Canc Res Dev Ctr, Cellular & Mol Immunol Sect, Lab Expt Immunol, NIH, Bldg 560, Rm 31-93, Frederick, MD 21702 USA. NCI, Frederick Canc Res Dev Ctr, Cellular & Mol Immunol Sect, Lab Expt Immunol, NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, NIH, Frederick, MD 21702 USA. Kanazawa Univ, Canc Res Inst, Dept Mol Oncol, Kanazawa, Ishikawa 920, Japan. Young HA NCI, Frederick Canc Res Dev Ctr, Cellular & Mol Immunol Sect, Lab Expt Immunol, NIH, Bldg 560, Rm 31-93, Frederick, MD 21702 USA.
    1. Year: 2001
  2. Journal: Journal of Immunology
    1. 166
    2. 12
    3. Pages: 7104-7111
  4. Type of Article: Article
  1. Abstract:

    Ligands for peroxisome proliferator-activated receptor gamma (PPAR gamma), such as 15-deoxy-Delta (12,14) PGJ(2) (15d- PGJ(2)) have been proposed as a new class of antiinflammatory compounds with possible clinical applications. As there is some controversy over the inhibitory effects of 15d-PGJ2 on chemokine gene expression, we investigated whether 15d-PGJ2 itself affected chemokine gene expression in human monocytes/macrophages and two monocytic cell lines. Here we demonstrate that the 15d-PGJ2 can induce IL-8 gene expression. In contrast, monocyte chemoattractant protein-1 gene expression was suppressed by 15d-PGJ2, while the expression of RANTES was unaltered. Furthermore, concomitant treatment of monocytes/macrophages with 15d-PGJ(2) (2.5 x 10(-6) M) potentiated LPS-induced gene expression of IL-8 mRNA, but suppressed PMA-induction of IL-8 mRNA. In addition, treatment of U937 and THP-1 cells with 15d-PGJ(2) also resulted in induction of IL-8 gene expression. Further studies demonstrated that 15d-PGJ2 regulated IL-8 gene expression via a ligand- specific and PPAR gamma -dependent pathway. Our observations revealed a previous unappreciated function and mechanism of 15d-PGJ(2)-mediated regulation of cytokine gene expression in monocytes/macrophages.

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