Ellagic acid mediated attenuation of store operated calcium entry alters cytokine expression in Jurkat T cells

Calcium is a ubiquitous second messenger regulating a myriad of cellular processes including proliferation, gene expression, and apoptosis. Agents that can modulate Ca 2+ homeostasis are being extensively explored as potential chemotherapeutic agents. Ellagic acid (EA), a polyphenolic compound found in many fruits and plant extracts, has been known to possess anticarcinogenic and anti‐inflammatory properties. EA is thought to modulate Ca 2+ homeostasis by enhancing sarcoplasmic endoplasmic reticulum ATPase pump (SERCA) activity, however effects of EA on Ca 2+ signaling is not clearly understood. In order to study this relationship, we measured changes in Ca 2+ transients in Jurkat T‐cells pretreated with EA (30 μM, 12 h). EA‐treated Jurkat T cells were challenged with SERCA inhibitor, thasipargin (TG) (2 μM). The amplitude of TG‐induced Ca 2+ transient in the EA‐treated cells was 30% lower than vehicle control cells. The depletion of ER‐stores signals activation of store‐operated Ca 2+ entry (SOCE) channels, resulting in Ca 2+ influx. EA‐pretreatment induced a concentration‐dependent decrease in store‐operated Ca 2+ entry in Jurkat T‐cells. Since expression of certain cytokines is directly dependent on Ca 2+ influx, we measured the levels of IL‐2 and INFγ in EA‐treated Jurkat T cells. Indeed, EA‐treated resulted in a significant decrease in IL‐2 and INFγ expression. These results link EA‐mediated attenuation of Ca 2+ influx to altered cytokine expression. These results indicate the anti‐inflammatory effects of EA could be attributed to its ability to attenuate store operated Ca 2+ influx.