Upregulation of interleukin-8 expression by prostaglandin D2 metabolite 15-deoxy-delta12, 14 prostaglandin J2 (15d-PGJ2) in human THP-1 macrophages
- 作者：Fu ; Yuchang ; Luo ; Nanlan ; Lopes-Virella ; Maria F.
- 关键词：Interleukin-8 ; 15-Deoxy-delta12 ; 14 prostaglandin J2 ; THP-1 macrophage ; Atherosclerosis
- 刊名：Atherosclerosis
- 出版年：2002
- 期刊代码：28_00219150
- 类别：med
- 出版时间：January, 2002
- 卷：160
- 期：1
- 页码：11-20
- 文件大小：444 K
摘要
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.