Tat-GSTpi suppresses inflammatory responses by regulating ROS/MAPKs/apoptosis signaling pathways
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Glutathione S-transferase pi (GSTpi) is a phase II detoxifyingenzyme that plays key roles in cellular processes. In a previousstudy, we have reported that cell permeable Tat-GSTpi canprotect 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 investigatethe one of plausible protective mechanism involved anti-inflammatoryeffect of GSTpi using lipopolysaccharide (LPS)- and12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced macrophagesand an animal model. It was revealed that cell permeableTat-GSTpi fusion protein markedly reduced reactiveoxygen species (ROS) and DNA injury in LPS-treated cells andtransduced protein showed not only inhibition of the regulationof 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 animalmodel by inhibition the COX-2, iNOS expression and cytokines. Those results indicate that GSTpi plays a role in antagonizingLPS- and TPA-induced inflammation, suggesting GSTpi has thepotential to serve as a therapeutic treatment for inflammatoryrelated diseases.
Abstract
Glutathione S-transferase pi (GSTpi) is a phase II detoxifyingenzyme that plays key roles in cellular processes. In a previousstudy, we have reported that cell permeable Tat-GSTpi canprotect 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 investigatethe one of plausible protective mechanism involved anti-inflammatoryeffect of GSTpi using lipopolysaccharide (LPS)- and12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced macrophagesand an animal model. It was revealed that cell permeableTat-GSTpi fusion protein markedly reduced reactiveoxygen species (ROS) and DNA injury in LPS-treated cells andtransduced protein showed not only inhibition of the regulationof 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 animalmodel by inhibition the COX-2, iNOS expression and cytokines. Those results indicate that GSTpi plays a role in antagonizingLPS- and TPA-induced inflammation, suggesting GSTpi has thepotential to serve as a therapeutic treatment for inflammatoryrelated diseases.