Tat-GSTpi suppresses inflammatory responses by regulating ROS/MAPKs/apoptosis signaling pathways.

Glutathione S-transferase pi (GSTpi) is a phase II detoxifying enzyme that plays key roles in cellular processes. In a previous study, we have reported that cell permeable Tat-GSTpi can protect dopaminergic neurons against cell death. However, the precise roles of GSTpi in inflammation remain to be elucidated. Thus, the objective of present study is to investigate the one of plausible protective mechanism involved anti-inflammatory effect of GSTpi using lipopolysaccharide (LPS)- and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced macrophages and an animal model. It was revealed that cell permeable Tat-GSTpi fusion protein markedly reduced reactive oxygen species (ROS) and DNA injury in LPS-treated cells and transduced protein showed not only inhibition of the regulation of mitogen-activated protein kinase (MAPK) and Caspase-9, but also decrease of COX-2 and iNOS expressions. Furthermore, Tat-GSTpi ameliorated skin inflammation in an animal model by inhibition the COX-2, iNOS expression and cytokines. Those results indicate that GSTpi plays a role in antagonizing LPS- and TPA-induced inflammation, suggesting GSTpi has the potential to serve as a therapeutic treatment for inflammatory related diseases.