OBJECTIVE To investigate the effects of peroxisome proliferator-activated receptors (PPARs)--fenofibrate and pioglitazoneon tumor necrosis factor-α (TNF-α) expression in cardiac myocytes of neonatal rat. The possible mechanism of action was explored. METHODS Primary cultures of cardiac myocytes were prepared from 1 - 3 day old Wistar rats, and then the myocytes were exposed to lipopolysac-charide (LPS) and fenofibrate and pioglitazone at different concentrations. RT-PCR and EL1SA were used to measure TNF-α expression in cultured cardiac myocytes. Transient transfection of TNF-α promoter with or without nuclear factor-kappaB (NF-icB) binding site to cardiac myocytes was performed. RESULTS Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNF-α mRNA and protein expression in dose-dependent manner. Proportional supression of TNF-α promoter activity was observed when the myocytes were transiently transfected with whole length of TNF-α promoter ( - 721/ +17) after being stimulated with LPS and fenofibrate or pioglitazone, whereas no change of the promoter activity was observed with the transfection of TNF-α reporter with deletion of NF-icB binding site ( - 182/ + 17) . CONCLUSION Fenofibrate and pioglitazone inhibit cardiac TNF-a expression and appear to play a role in anti-inflammation. The mechanism may be partly involved in suppression of NF-κB pathway.
Key words
fenofibrate /
pioglitazone /
tumor necrosis factor-α /
cardiac myocytes /
activators /
nuclear factor-kappaB
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