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-α) and PPAR ligands on the expression of PPARs in HL-1 cardiomyocytes. Materials and methods: HL-1 cardiomyocytes were incubated with and without TNF-α (1, 10, 25 and 50 ng mL^-1) or PPAR ligands (rosiglitazone, pioglitazone and fenofibrate) at concentrations of 0.1, 1 and 10 μm for 24 h. The cells also received SN-50 (NF-κB inhibitor, 50 μg mL^-1), ascorbic acid (100 μm) and coenzyme Q₁₀ (10 μm) alone or combined with TNF-α. Results: Using reverse transcriptase-polymerase chain reaction and Western blot, we found that incubation of TNF-α (50 ng mL^-1) for 24 h decreased PPAR-α, but increased PPAR-γ without altering PPAR-δ. These effects were not changed by co-administration of SN-50. However, co-administration of ascorbic acid prevented the effect of TNF-α both on PPAR-α and PPAR-γ. Coenzyme Q₁₀ partially attenuated the effect of TNF-α on PPAR-γ but did not alter its effect on PPAR-α. The administration of rosiglitazone (10 μm) and pioglitazone (10 μm) for 24 h increased PPAR-γ mRNA, but did not alter PPAR-α or PPAR-δ. Moreover, fenofibrate (0.1, 1 and 10 μm) increased PPAR-γ without any effects on PPAR-α or PPAR-δ. Conclusions: Oxidative stress causes the regulations of PPAR-α and PPAR-γ in the TNF-α-treated cardiomyocytes. The up-regulation of PPAR-γ by PPAR ligands may contribute to their anti-inflammation effects.