Oncotarget

Research Papers: Immunology:

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

Shaqiu Zhang, Tamer al-Maghout, Rosi Bissinger, Ni Zeng, Lisann Pelzl, Madhuri S. Salker, Anchun Cheng _, Yogesh Singh and Florian Lang

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Oncotarget. 2017; 8:89500-89514. https://doi.org/10.18632/oncotarget.20032

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Abstract

Shaqiu Zhang1,2,6,*, Tamer al-Maghout2,6,*, Rosi Bissinger2,6, Ni Zeng2,3,6, Lisann Pelzl2,6, Madhuri S. Salker2,4,6, Anchun Cheng1,**, Yogesh Singh2,5,6,** and Florian Lang2,6**

1 Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, Sichuan, P.R. China

2 Department of Internal Medicine III, Tübingen University, Gmelinstraβe, Tübingen, Germany

3 Department of Cleft Lip and Palate Surgery, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China

4 Institute of Women’s Health, Tübingen University, Calwerstraβe, Tübingen, Germany

5 Institute of Medical Genetics and Applied Genomics, Tübingen University, Calwerstraβe, Tübingen, Germany

6 Institute of Physiology I, Tübingen University, Gmelinstraβe, Tübingen, Germany

* Equal contributions thus sharing first authorship

** Equal contributions thus sharing last authorship

Correspondence to:

Anchun Cheng, email:

Yogesh Singh, email:

Florian Lang, email:

Keywords: Murine CD4+ T cells, human leukaemic T cell lymphoblasts, EGCG, SOCE, miR-15b, Immunology and Microbiology Section, Immune response, Immunity

Received: January 10, 2017 Accepted: July 26, 2017 Published: October 27, 2017

Abstract

CD4+ T cells are key elements in immune responses and inflammation. Activation of T cell receptors in CD4+ T cells triggers cytosolic Ca2+ release with subsequent store operated Ca2+ entry (SOCE), which is accomplished by the pore forming Ca2+ release activated Ca2+ (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 Ca2+ 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 Ca2+ entry into murine and human T cells, an effect accomplished at least in part by up-regulation of miR-15b.


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