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12,1412,14 Prostaglandin J21 ,2
*
Cellular and Molecular Immunology Section, Laboratory of Experimental Immunology, and
Laboratory of Molecular Immunoregulation, Division of Basic Science, National Cancer Institute-Frederick Cancer Research Development Center, National Institute of Health, Frederick, MD 21702; and
Department of Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
Ligands for peroxisome proliferator-activated receptor 
(PPAR), such as 15-deoxy-
12,14PGJ2
(15d-PGJ2) 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-PGJ2 (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-PGJ2 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-dependent pathway. Our observations
revealed a previous unappreciated function and mechanism of
15d-PGJ2-mediated regulation of cytokine gene expression in
monocytes/macrophages.
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