Effects of Peroxisome Proliferator-Activated Receptor-gamma on the Production of Tumor Necrosis Factor-alpha in Stimulated Human Monocoytes / 감염과화학요법

ABSTRACT

BACKGROUND: We evaluated the effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the production of tumor necrosis factor-alpha (TNF-alpha) and expression of nuclear factor-kappaB (NF-kappaB) in stimulated THP-1 cells, a human monocyte cell line. MATERIALS AND METHODS: We evaluated the cytotoxic effect of 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), one of natural PPAR-gamma ligands, using commercial cell proliferation assay. Cells were pretreated with 15d-PGJ(2) and then stimulated with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). The amount of TNF-alpha was measured by using commercial ELISA method. NF-kappaB activation was evaluated by Western blot analysis. RESULTS: 15d-PGJ(2) showed dose-dependent cytotoxic effect on the tested cells after 4 hr of treatment. Stimulation of cells by LPS or LTA induced TNF-alpha production. TNF-alpha production was markedly decreased in the cells pretreated with 15d-PGJ(2) compared to cells treated only with LPS or LTA in a dose-dependent manner. Pretreatment of 15d-PGJ(2) reduced LPS or LTA induced NF-kappaB expression in the nuclear extracts of THP-1 cells. CONCLUSION: 15d-PGJ(2) pretreatment decreased TNF-alpha production from the THP-1 cells stimulated by LPS or LTA, and this assumed to be associated with inhibition of NF-kappaB activation.