Proinflammatory cytokine and ligands modulate cardiac peroxisome proliferator-activated receptors.
BACKGROUND
Peroxisome proliferator-activated receptors (PPAR) mediate inflammatory processes and alter cardiac function. However, it is not clear whether inflammatory cytokines or PPAR ligands regulate PPARs in the cardiomyocytes to modulate cardiac functions. We investigated the effects of tumour necrosis factor-alpha (TNF-alpha) and PPAR ligands on the expression of PPARs in HL-1 cardiomyocytes.


METHODS
HL-1 cardiomyocytes were incubated with and without TNF-alpha (1, 10, 25 and 50 ng mL(-1)) or PPAR ligands (rosiglitazone, pioglitazone and fenofibrate) at concentrations of 0.1, 1 and 10 microM for 24 h. The cells also received SN-50 (NF-kappaB inhibitor, 50 microg mL(-1)), ascorbic acid (100 microM) and coenzyme Q10 (10 microM) alone or combined with TNF-alpha.


RESULTS
Using reverse transcriptase-polymerase chain reaction and Western blot, we found that incubation of TNF-alpha (50 ng mL(-1)) for 24 h decreased PPAR-alpha, but increased PPAR-gamma without altering PPAR-delta. These effects were not changed by co-administration of SN-50. However, co-administration of ascorbic acid prevented the effect of TNF-alpha both on PPAR-alpha and PPAR-gamma. Coenzyme Q10 partially attenuated the effect of TNF-alpha on PPAR-gamma but did not alter its effect on PPAR-alpha. The administration of rosiglitazone (10 microM) and pioglitazone (10 microM) for 24 h increased PPAR-gamma mRNA, but did not alter PPAR-alpha or PPAR-delta. Moreover, fenofibrate (0.1, 1 and 10 microM) increased PPAR-gamma without any effects on PPAR-alpha or PPAR-delta.


CONCLUSIONS
Oxidative stress causes the regulations of PPAR-alpha and PPAR-gamma in the TNF-alpha-treated cardiomyocytes. The up-regulation of PPAR-gamma by PPAR ligands may contribute to their anti-inflammation effects.
Lee
T-I
TI
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan.
Kao
Y-H
YH
Chen
Y-C
YC
Chen
Y-J
YJ
D001205:Ascorbic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism*
D047492:Peroxisome Proliferator-Activated Receptors; D014409:Tumor Necrosis Factor-alpha; D014451:Ubiquinone; D001205:Ascorbic Acid