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Effects of Peroxisome Proliferator-Activated Receptor-? on the Production of Tumor Necrosis Factor-? in Stimulated Human Monocoytes
Eun-Young Kwon1, Chulmin Park1, Jae-Cheol Kwon2, Si-Hyun Kim2, Sun Hee Park2, Su-Mi Choi2, Dong-Gun Lee2, Jin-Hong Yoo2, and Jung-Hyun Choi2
1Catholic Research Institutes of Medical Science, 2Department of Internal Medicine, Division of Infectious Diseases, College of Medicine, Catholic University of Korea, Seoul, Korea
Vol.42 Num.5 (p291~295)
Background: We evaluated the effects of peroxisome proliferator-activated receptor-? (PPAR-?) on the production of tumor necrosis factor-? (TNF-?) and expression of nuclear factor-?B (NF-?B) in stimulated THP-1 cells, a human monocyte cell line.
Materials and Methods: We evaluated the cytotoxic effect of 15-Deoxy-?12,14- prostaglandin J2 (15d-PGJ2), one of natural PPAR-? ligands, using commercial cell proliferation assay. Cells were pretreated with 15d-PGJ2 and then stimulated with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). The amount of TNF-? was measured by using commercial ELISA method. NF-?B activation was evaluated by Western blot analysis.
Results: 15d-PGJ2 showed dose-dependent cytotoxic effect on the tested cells after 4 hr of treatment. Stimulation of cells by LPS or LTA induced TNF-? production. TNF-? production was markedly decreased in the cells pretreated with 15d-PGJ2compared to cells treated only with LPS or LTA in a dose-dependent manner. Pretreatment of 15d-PGJ2 reduced LPS or LTA induced NF-?B expression in the nuclear extracts of THP-1 cells.
Conclusion: 15d-PGJ2 pretreatment decreased TNF-? production from the THP-1 cells stimulated by LPS or LTA, and this assumed to be associated with inhibition of NF-?B activation.
Keywords : Peroxisome proliferator-activated receptor-? (PPAR-?), Tumor necrosis factor (TNF)-?, Nuclear factor-?B (NF-?B)