Infect Chemother.  2010 Oct;42(5):291-295. 10.3947/ic.2010.42.5.291.

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

• Kwon EY
• Park C
• Kwon JC
• Kim SH
• Park SH
• Choi SM
• Lee DG
• Yoo JH
• Choi JH

• KMID: 1806891
• DOI: http://doi.org/10.3947/ic.2010.42.5.291

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.

Keyword

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma); Tumor necrosis factor (TNF)-alpha; Nuclear factor-kappaB (NF-kappaB)

MeSH Terms

Blotting, Western
Cell Line
Cell Proliferation
Enzyme-Linked Immunosorbent Assay
Humans
Ligands
Lipopolysaccharides
Monocytes
NF-kappa B
Peroxisomes
Teichoic Acids
Tumor Necrosis Factor-alpha
Ligands
Lipopolysaccharides
NF-kappa B
Teichoic Acids
Tumor Necrosis Factor-alpha

Figure

• 

  Figure 1 Effects of different concentrations of 15d-PGJ2 on the cell viability in THP-1 cells (1×104). Cell viability was assessed by WST-1 assay as described in the Materials and Methods section. Data are expressed as inhibition percentage compared to the untreated cells.

• 

  Figure 2 Effects of 15d-PGJ2 on TNF-α production in THP-1 cells. TNF-α production of THP-1 cells were detected by ELISA method. Cells (1×106 cells) were stimulated with LPS (100 ng/mL) (A) or LTA (1 µg/mL) (B) for 4 hr. 15d-PGJ2 was added 4 hr before stimulation. Con, control; LPS, lipopolysaccharide; LTA; lipoteichoic acid (aP<0.001 compared with control; bP<0.05, cP<0.001 compared with LPS or LTA stimulated cells).

• 

  Figure 3 Effects of 15d-PGJ2 on NF-κB activity in THP-1 cells. Activity of NF-κB in nuclear extracts of THP-1 cells were detected by Western blot analysis. Cells (7×106 cells) were stimulated with LPS (100 ng/mL) (A) or LTA (1 µg/mL) (B) for 2 hr. 15d-PGJ2 was added 4 hr before stimulation. Con, control; LPS, lipopolysaccharide; LTA; lipoteichoic acid; GAPDH, glyceraldehydes-3-phsphate dehydrogenase.

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