Purified Eicosapentaenoic Acid Induces Prolonged Survival of Cardiac Allografts and Generates Regulatory T Cells

Peroxisome Proliferator-Activated Receptor α and γ Agonists Together with TGF-β Convert Human CD4+CD25− T Cells into Functional Foxp3+ Regulatory T Cells

“…Hontecillas and Bassaganya-Riera (36) reported that PPARg-deficient Tregs have an impaired ability to prevent effector T cellinduced colitis. Furthermore, Iwami et al (35) showed that the PPARg agonist eicosapentaenoic acid induces Tregs and prolongs the survival of cardiac allografts. However, the mechanism by which PPARg enhances Treg activity remains unknown.…”

“…Furthermore, PPARa and PPARg agonists were reported to have immunomodulatory functions, such as inhibition of functional maturation and migration of dendritic cells (DCs) and a preferential shift from Th1-dominant toward Th2-dominant responses (27)(28)(29)(30)(31)(32)(33). In addition, some studies using mice showed that PPARg agonist induces Tregs and prolongs the survival of cardiac allografts in vivo, whereas deficiency of PPARg in Tregs impairs their ability to prevent trinitrobenzene sulfonic acid-induced colitis in vivo (34)(35)(36). These results suggest an important role for PPARg in the induction and function of Tregs.…”

Immunomodulatory effects of eicosapentaenoic acid through induction of regulatory T cells

“…We investigated the effects of purified EPA on the alloimmune response in a murine model of transplantation of fully mismatched cardiac grafts [79]. In the study, one high dose of purified EPA given the day of transplantation induced marked prolongation of graft survival in a dose-dependent manner.…”

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“…3 Iwami and associates demonstrated that EPA administration in the major histocompatibility complex-mismatched C57BL/10 to CBA murine cardiac allograft model achieved prolonged allograft survival accompanying gene ration of regulatory T cells in grafts. 4 They also showed that peroxisome proliferator-activated receptor that has been shown to be a nuclear receptor for EPA5, 6 is indispensable for the immuno modulatory effect of EPA. In addition Ye and associates demonstrated that cardiac allografting from BALB/c to C57BL/6 combination in mice with EPA exhibited significant prolongation of the graft survival by disrupting the balance between regulatory T cells and T-helper 17 cells.…”

“…To obtain a tolerance model on the day of transplant the recipients were given 1 intraperitoneal injection of 1.0 g/kg of purified eicosapentaenoic acid (EPA) (Mochida Pharmaceutical, Tokyo, Japan). 4 miRNA isolation from cardiac graft tissue miRNA was isolated from the cardiac grafts and immersed in RNAlater (Ambion Austin, TX, USA) soon after recovery using the miRNeasy kit (Qiagen Valencia, CA, USA) according to the manufacturer's protocol as described previously. 10 The miRNA quality and quantity were estimated using a NanoDrop 1000 spectrophotometer (Thermo Scientific Inc. Waltham, MA, USA) and an Agilent 2100 Bioanalyzer (Agilent Technologies Santa Clara, CA, USA).…”