Curcumin suppresses T cell activation by blocking Ca2+ mobilization and nuclear factor of activated T cells (NFAT) activation.
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 Ca(2+) mobilization with IC(50) = ∼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 Ca(2+) 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.
Technologietransfer (T010), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Christian
C
Kliem
Tumorimmunology Program (D030), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Anette
A
Merling
Tumorimmunology Program (D030), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Marco
M
Giaisi
Tumorimmunology Program (D030), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Rebecca
R
Köhler
Tumorimmunology Program (D030), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Peter H
PH
Krammer
Tumorimmunology Program (D030), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. Electronic address: m.li-weber@dkfz-heidelberg.de.
Min
M
Li-Weber
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D003474:Curcumin / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; D016572:Cyclosporine; D003474:Curcumin; D002118:Calcium