Calcium/calmodulin-dependent protein kinase II regulates IL-10 production by human T lymphocytes: a distinct target in the calcium dependent pathway

Molecular Immunology
Stavroula BoubaliF Paliogianni

Abstract

Calcium (Ca2+) plays an essential role in lymphocyte activation and differentiation by affecting signaling pathways leading to cytokine production. Among the enzymes responding to calcium increase, Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been involved in anergy with a still poorly characterized role. IL-10 produced by different T lymphocyte subpopulations is critical mediator of tolerance. We tested the hypothesis that CaMKII may be involved in IL-10 production. We report that CaMKII upregulates IL-10 production by primary human T lymphocytes stimulated through the antigen receptor or bypassing that. Overexpression of constitutively active mutant forms of Calcineurin or CaMKII specifically increase IL-10 protein product and IL-10 mRNA accumulation in T lymphocytes. By cotransfecting constitutively active CaMKII with luciferase reporter plasmids carrying specific fragments or the whole IL-10 promoter, we show that CaMKII specifically activates IL-10 promoter activity, whereas it inhibits IL-2 and IL-4 promoter. This effect is mediated by the first 500 bp fragment, which contains binding sites for Myocyte Enhancer Factor-2 (MEF2). A constitutively active mutant of CaMKII activated a luciferase reporter plasmid un...Continue Reading

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Citations

Jan 16, 2014·BMC Cardiovascular Disorders·Chenxi ZhaoMotoji Sawabe
Jan 29, 2014·European Journal of Immunology·Saskia ZieglerIsabelle Bekeredjian-Ding
Aug 21, 2013·International Reviews of Immunology·Jens Vent-SchmidtMegan K Levings
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Jan 18, 2018·Oncotarget·Xiao ChenJia Liu
Aug 9, 2020·Scandinavian Journal of Immunology·Shrikant S KolanBjørn Steen Skålhegg
Jul 12, 2020·International Journal of Molecular Sciences·J Kenneth Hoober
Jul 30, 2020·Bioscience Reports·Michael J PattisonJ Simon C Arthur
Aug 8, 2020·Frontiers in Physiology·Carolina Victoria Cruz JunhoMarcela Sorelli Carneiro-Ramos
Sep 7, 2019·International Journal of Molecular Sciences·Maria Rosaria RuscianoAngela Serena Maione
Jan 11, 2020·Frontiers in Immunology·J Kenneth HooberRobert Cote
Aug 14, 2020·The Journal of Clinical Investigation·Eros Di GiorgioWayne W Hancock
May 1, 2021·International Journal of Molecular Sciences·Kinga SałaciakKarolina Pytka

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