PPARα Ameliorates Experimental Autoimmune Myocarditis By Inhibiting IL-17 Cytokine Expression

Objective This study was designed to explore the function and the effect of PPARa on EAM rats and the mechanism of it. Methods Experimental autoimmune myocarditis (EAM) rats were injected with porcine cardiac myosin and complete Freund’s adjuvant in double feet. Fenofibrate(100/200 mg/kg/d) or vehic was administered orally from DO to D17, while physiological saline was administered, orally from DO to D17 On control group. On day 17, the severity of myocarditis was evaluated by hematoxylin and eosin (HE) staining, the mRNA expression of Atrium natriuretic peptide (ANP)and brain natriuretic peptide(BNP), Th17-type cytokines (IL-17) and the related cytokines(IL-6,TGF-β) were determined by Quantative RT-PCR, and the serum level of IL-17 were measured by ELISA.PPARa protein determined by western blot and its Mrna determined by RT-PCR.In addition,CD4T cells isolated from rats spleen cutured with fenobrate(PPARa agonist) and mk886(a inhibitor of PPARa) in different combination. And detected the level of IL-17 by Quantative RT-PCR, ELISA and FASC. Results HW/BW and the relative expression of ANP、BNP started to rise on day 14(2W),presenting a highest level on day 21(3w). The relative expression of IL-17 、IL-1 presented a higher leval on day 14the.HE staining showed that a large number of inflammatory cells infiltrated cardiac muscle tissues, which was the most serious stage on day 14 of the whole disease course.At the same time, PPARa present a lower level on day 14 but a higher level on day 21.The expression of ANP、BNP、HW/BW were elevated in EAM group but decressed in fenofibrate group on day 17. In addition, treatment with fenofibrate decreased the expression of Th17-type cytokines (IL-17) and the related cytokines(IL-6,TGF-β).In cultured spleen cells, The IL-17 and its related cytokines presented a low level in the group cultured with fenobrate than the group cultured with fenobrate and mk886.Conclusions Activiting PPARA α can inhibiting IL-17 cytokine which ameliorates the experimental autoimmune myocarditis.