Effect of peroxisome proliferator-activated receptor activators on tumor necrosis factor-alpha expression in neonatal rat cardiac myocytes.
OBJECTIVE
To investigate the effect of peroxisome proliferator-activated receptor-alpha (PPAR alpha) and PPAR gamma activators on tumor necrosis factor-alpha (TNFalpha) expression in neonatal rat cardiac myocytes.


METHODS
Primary cultures of cardiac myocytes from 1- to 3-day-old Wistar rats were prepared, and myocytes were exposed to lipopolysaccharide (LPS) and varying concentrations of PPAR alpha or PPAR gamma activator (fenofibrate or pioglitazone). RT-PCR and ELISA were used to measure TNFalpha, PPAR alpha, and PPAR gamma expression in cultured cardiac myocytes. Transient transfection of TNFalpha promoter with or without nuclear factor-kappaB (NF-kappaB) binding site to cardiac myocytes was performed.


RESULTS
Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNFalpha mRNA and protein expression in a dose-dependent manner. However, no significant changes were observed on PPAR alpha or PPAR gamma mRNA expression when cardiac myocytes were pretreated with fenofibrate or pioglitazone. Proportional suppression of TNFalpha promoter activity was observed when myocytes was transiently transfected with whole length of TNFalpha promoter (-721/+17) after being stimulated with LPS and fenofibrate or pioglitazone, whereas no change of promoter activity was observed with transfection of TNFalpha reporter construct in deletion of NF-kappaB binding site (-182/+17).


CONCLUSIONS
PPAR alpha and PPAR gamma activators may inhibit cardiac TNFalpha expression but not accompanied by change of PPAR alpha or PPAR gamma mRNA expression. Therefore PPAR alpha and PPAR gamma activators appear to play a role in anti-inflammation. The mechanism may partly be involved in suppression of the NF-kappaB pathway.
Ye
Ping
P
Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing 100853. yeping@sina.com
Fang
Hong
H
Zhou
Xin
X
He
Yan-li
YL
Liu
Yong-xue
YX
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D011345:Fenofibrate / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D047493:PPAR alpha / Q000096:biosynthesis* / Q000235:genetics; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D008070:Lipopolysaccharides; D016328:NF-kappa B; D047493:PPAR alpha; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D011345:Fenofibrate; D000077205:Pioglitazone