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Proinflammatory cytokine and ligands modulate cardiac peroxisome proliferator‐activated receptors
Author(s) -
Lee TI.,
Kao YH.,
Chen YC.,
Chen YJ.
Publication year - 2009
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2008.02062.x
Subject(s) - peroxisome proliferator activated receptor , fenofibrate , rosiglitazone , endocrinology , medicine , pioglitazone , ppar agonist , receptor , peroxisome proliferator activated receptor alpha , chemistry , peroxisome , proinflammatory cytokine , coenzyme q10 , biology , biochemistry , inflammation , nuclear receptor , transcription factor , gene , type 2 diabetes , diabetes mellitus
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 µ m for 24 h. The cells also received SN‐50 (NF‐κB inhibitor, 50 µg mL −1 ), ascorbic acid (100 µ m ) and coenzyme Q 10 (10 µ m ) 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 Q 10 partially attenuated the effect of TNF‐α on PPAR‐γ but did not alter its effect on PPAR‐α. The administration of rosiglitazone (10 µ m ) and pioglitazone (10 µ m ) for 24 h increased PPAR‐γ mRNA, but did not alter PPAR‐α or PPAR‐δ. Moreover, fenofibrate (0·1, 1 and 10 µ m ) 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.