-Prostaglandin J2 in Experimental Autoimmune Encephalo- myelitis

Peroxisome proliferator-activated receptor (PPAR) is a family of nuclear receptor transcription factors that regulates immune cell growth, differentiation and homeostasis. We and others have shown earlier that in vivo treatment with PPAR , / or agonists ameliorates experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). In this study we show that C57BL/6 mice induced to develop EAE display augmented neural antigen-specific T cell response that was inhibited by PPAR agonist 15-deoxy12,14 -Prostaglandin J2 (15d-PGJ2). EAE mice showed elevated expression of IFN and IL-17 in the CNS and lymphoid organs compared to naïve mice that decreased significantly following treatment with 15d-PGJ2. EAE mice also expressed elevated levels of IL-12 and IL-23 that decreased after treatment with 15d-PGJ2. 15d-PGJ2 also attenuated the expression of IFN , IL-17, IL-12 and IL-23 in neural antigenspecific spleen cells ex vivo and in vitro. Moreover, EAE mice expressed low levels of IL-4, IL-10 and PPAR compared to naïve that increased significantly following treatment with 15d-PGJ2. However, 15d-PGJ2 failed to change the expansion of CD4 + CD25 + Foxp3 + Treg cells in EAE. These findings suggest that 15d-PGJ2 differentially regulates CD4 + T helper cell subset responses in EAE.