Inhibition of T cell activation by the phytochemical piperine (50.35)

Abstract

Abstract Piperine, a major alkaloid of the fruits of black and long pepper plants, exhibits anti-inflammatory activity both in vitro and in vivo. Although the effect of piperine on T cell function is not yet known, we hypothesized that piperine might inhibit T cell processes involved in inflammation. We therefore examined the effect of piperine on T cell proliferation, activation marker expression, and cytokine production. Cellular proliferation was determined by tritiated-thymidine incorporation and Oregon Green® 488 staining while activation marker expression was assessed by flow cytometry. Cytokine production and intracellular signalling pathways were examined by ELISA and Western blot analysis, respectively. Piperine inhibited T cell proliferation in a dose-dependent manner without affecting T cell viability. Piperine also inhibited expression of the T cell activation markers CD25, CD69, and CTLA-4, as well as production of the cytokines IFN-γ, IL-2, IL-4, and IL-17. Phosphorylation of extracellular signal-regulated kinase (ERK) and inhibitor of κBα (IκBα) was diminished in T cells stimulated in the presence of piperine, indicating that piperine affects signalling pathways involved in T cell activation. Collectively, these data suggest that piperine warrants further investigation as a possible immunosuppressive agent for the treatment of T cell-mediated inflammation. Supported by NSERC and CIHR.