Curcumin Suppresses T Cell Activation by Blocking Ca2+ Mobilization and Nuclear Factor of Activated T Cells (NFAT) Activation

• Published in: The Journal of biological chemistry 2012-03, Vol.287 (13), p.10200-10209
• Main Authors: Kliem, Christian, Merling, Anette, Giaisi, Marco, Köhler, Rebecca, Krammer, Peter H., Li-Weber, Min
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Calcium - metabolism; Calcium Signaling; Calcium Signaling - drug effects; Calcium Signaling - physiology; Curcumin - pharmacology; Cyclosporine - pharmacology; Cytokine; Cytokines - biosynthesis; Cytokines - genetics; Drug Action; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Humans; Immunology; Immunosuppressive Agents - pharmacology; Jurkat Cells; Lymphocyte Activation - drug effects; Lymphocyte Activation - physiology; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB (NF-κB); NFAT Transcription Factor; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; Oxidation-Reduction - drug effects; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; T Cell; T-Lymphocytes - cytology; T-Lymphocytes - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.318733

Curcumin is the active ingredient of the spice turmeric and has been shown to have a number of pharmacologic and therapeutic activities including antioxidant, anti-microbial, anti-inflammatory, and anti-carcinogenic properties. The anti-inflammatory effects of curcumin have primarily been attributed to its inhibitory effect on NF-κB activity due to redox regulation. In this study, we show that curcumin is an immunosuppressive phytochemical that blocks T cell-activation-induced Ca2+ mobilization with IC50 = ∼12.5 μm and thereby prevents NFAT activation and NFAT-regulated cytokine expression. This finding provides a new mechanism for curcumin-mediated anti-inflammatory and immunosuppressive function. We also show that curcumin can synergize with CsA to enhance immunosuppressive activity because of different inhibitory mechanisms. Furthermore, because Ca2+ is also the secondary messenger crucial for the TCR-induced NF-κB signaling pathway, our finding also provides another mechanism by which curcumin suppresses NF-κB activation. Curcumin can overcome CsA resistance. However, the molecular mechanism is unknown. Curcumin blocks T cell stimulation-induced Ca2+ mobilization and thereby prevents NFAT activation, a mechanism different from CsA. Curcumin is an immunosuppressive phytochemical that blocks Ca2+ signaling. The study demonstrates for the first time that curcumin is a potent inhibitor of NFAT activation via blocking Ca2+ signaling in T cells.