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Upregulation of interleukin-8 expression by prostaglandin D2 metabolite 15-deoxy-delta12, 14 prostaglandin J2 (15d-PGJ2) in human THP-1 macrophages

  • Yuchang Fu
    Correspondence
    Corresponding author. Tel.: +1-843-577-5011x6800; fax: +1-843-876-5133
    Affiliations
    Room 520, Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Strom Thurmond Biomedical Center, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29403-5729, USA
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  • Nanlan Luo
    Affiliations
    Room 520, Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Strom Thurmond Biomedical Center, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29403-5729, USA
    Search for articles by this author
  • Maria F Lopes-Virella
    Affiliations
    Room 520, Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Strom Thurmond Biomedical Center, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29403-5729, USA

    Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC 29403, USA
    Search for articles by this author

      Abstract

      Interleukin-8 (IL-8) is one of cytokines detected at sites of inflammation and in macrophage-foam cells of atherosclerotic lesions. The expression of IL-8 gene can be induced in cholesterol loaded THP-1 macrophages by oxidized low density lipoprotein. We report for the first time that the expression of human IL-8 gene in THP-1 macrophages is upregulated in a time- and concentration-dependent manner by prostaglandin D2 metabolite 15-deoxy-delta12, 14 prostaglandin J2 (15d-PGJ2), which is a natural ligand for activation of peroxisome proliferator-activated receptor-gamma transcription factor. Studies to identify the signal transduction pathways involved showed that IL-8 upregulation-mediated by 15d-PGJ2 was markedly inhibited when the THP-1 macrophages were incubated with a highly selective and cell-permeable inhibitor of the mitogen-activated protein kinase (MAPK) signaling pathway, 2′-amino-3′-methoxyflavone (PD98059). This inhibition was concentration-dependent, suggesting that 15d-PGJ2 regulates the expression of IL-8 gene in THP-1 macrophages through a MAPK signaling pathway. In contrast, THP-1 macrophages when treated with pyrrolidine dithiocarbamate, an anti-oxidant and the selective inhibitor for nuclear factor κB, showed an enhanced 15d-PGJ2-mediated upregulation of IL-8 gene expression. The data presented in this report may contribute to unravel some of the mechanisms behind the inflammatory component of atherosclerosis.

      Keywords

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