Curcumin may inhibits t cell activation through store-operated Ca2+ entry channels and k+ channels

Ca²⁺-release activated Ca²⁺ channel (CRAC)-mediated increase in cytoplasmic Ca²⁺ concentration (D[Ca²⁺]_c) is a critical early step of signals for the activation of lymphocytes. Also, the voltage-gated K⁺ channel (K_v) and intermediate-conductance Ca²⁺-activated K⁺ channel (IKCa1/SK4) draw attention as pharmacological targets for regulating immune responses. Since polyphenolic agents have various ranges of anti-inflammatory or immunomodulatory effects, here we compared the effects of curcumin, rosmarinic acid, resveratrol and epigallocatechin gallate on the ionic currents through CRAC (I_CRAC), Kv (I_Kv), SK4 (I_SK4), and on the D[Ca²⁺]_c in Jurkat-T cells, using fura-2 spectrofluorimetry and patch clamp technique. Curcumin (10 mM) inhibited both anti-CD3 Ab-induced D[Ca²⁺]_c and thapsigargin-induced store-operated Ca²⁺ entry (SOCE) via CRAC. Ferulic acid and vanillin, the metabolites of curcumin, had no effect on SOCE. Dose-dependent inhibition of I_CRAC by curcumin was confirmed in Jurkat T (IC₅₀, 5.9 mM) and the HEK-293 cells overexpressing Orai1 and STIM1 (IC₅₀, 0.6 mM). Also, curcumin potently inhibited both I_Kv (IC₅₀, 11.9 mM) and I_SK4 (IC₅₀, 4.2 mM). The other polyphenols (rosmarinic acid, resveratrol and epigallocatechin gallate at 10 – 30 mM) had no effect on SOCE, and showed only a partial inhibition of the K⁺ currents. In summary, among the tested polyphenolic agents, curcumin showed prominent inhibition of major ion channels in lymphocytes, which might contribute to the anti-inflammatory effects of curcumin when sufficient concentration is reached in vivo.