Epigallocatechin-3-gallate (EGCG) up-regulates miR-15b expression thus attenuating store operated calcium entry (SOCE) into murine CD4(+) T cells and human leukaemic T cell lymphoblasts

CD4(+) T cells are key elements in immune responses and inflammation. Activation of T cell receptors in CD4(+) T cells triggers cytosolic Ca(2+) release with subsequent store operated Ca(2+) entry (SOCE), which is accomplished by the pore forming Ca(2+) release activated Ca(2+) (CRAC) channel Orai1 and its regulator stromal cell-interaction molecule 2 (STIM2). Green tea polyphenol epigallocatechin-3-gallate (EGCG) acts as a potent anti-inflammatory and anti-oxidant agent for various types of cells including immune cells. However, how post-transcriptional gene regulators such as miRNAs are involved in the regulation of Ca(2+) influx into murine CD4(+) T cells and human Jurkat T cells through EGCG is not defined. EGCG treatment of murine CD4(+) T cells significantly down-regulated the expression of STIM2 and Orai1 both at mRNA and protein levels. Furthermore, EGCG significantly decreased SOCE in both murine and human T cells. EGCG treatment increased miRNA-15b (miR-15b) abundance in both murine and human T cells. Bioinformatics analysis reveals that miR-15b, which has a STIM2 binding site, is involved in the down-regulation of SOCE. Overexpression of miR-15b significantly decreased the mRNA and protein expression of STIM2 and Orai1 in murine T cells. Treatment of Jurkat T cells with 10 μM EGCG further decreased mTOR and PTEN protein levels. EGCG decreased mitochondrial membrane potential (MMP) in both human and murine T cells. In conclusion, the observations suggest that EGCG inhibits the Ca(2+) entry into murine and human T cells, an effect accomplished at least in part by up-regulation of miR-15b.