Naturally occurring 3 RS , 7 R , 11 R -phytanic acid suppresses in vitro T-cell production of interferon-gamma

摘要

Abstract BackgroundAmong the eight stereoisomers of phytanic acid (PA), the 3 RS , 7 R , 11 R -isomer is naturally occurring and is present in foods and the human body. PA is considered to have possible health benefits in the immune system. However, it remains undetermined whether these effects are elicited by the 3 RS , 7 R , 11 R -PA isomer, because previous studies used a commercially available PA whose isomer configuration is unknown. In this study, we synthesized a preparation of 3 RS , 7 R , 11 R -PA, and investigated its in vitro immunomodulatory effects, especially the T-cell production of interferon (IFN)-γ, which is associated with various autoimmune diseases. This study also investigated the effects of 3 RS , 7 R , 11 R -PA on NF-κB activity in order to address the mechanism of its immunomodulatory effects.MethodsMouse splenocytes and purified T-cells were stimulated with T-cell mitogens and incubated with 3 RS , 7 R , 11 R -PA, followed by evaluation of IFN-γ production. The effect of 3 RS , 7 R , 11 R -PA on NF-κB activity was also investigated using an A549 cell line with stable expression of an NF-κB-dependent luciferase reporter gene.Results3 RS , 7 R , 11 R -PA significantly reduced in vitro IFN-γ production at both the protein and mRNA levels, and was accompanied by decreased expression of T-bet, a key regulator of Th1 cell differentiation. The results indicated that NF-κB-mediated transcriptional activity was significantly decreased by 3 RS , 7 R , 11 R -PA and that GW6471, an antagonist of peroxisome proliferator activated receptor α (PPARα), abrogated the inhibitory effect of 3 RS , 7 R , 11 R -PA on NF-κB activity.ConclusionsThe present study suggests that 3 RS , 7 R , 11 R -PA is a functional and bioactive fatty acid, and has a potentially beneficial effect for amelioration of T-cell mediated autoimmune diseases. This study also indicates that interference in the NF-κB pathway via PPARα activation is a potential mechanism of the immunomodulatory effects of 3 RS , 7 R , 11 R -PA.