Inhibition of interleukin 10 transcription through the Smad2/3 signaling pathway by Ca21-activated K1channel KCa3.1 activation in human T-cell lymphoma HUT-78 cells s

Abstract

The hyperpolarization induced by intermediate-conductance Ca21-activated K1channel (KCa3.1) activation increases the driving force for Ca21influx, which generally promotes cell proliferation, migration, and cytokine production in immunocom-petent cells. Interleukin-10 (IL-10) from tumor-infiltrating lymphocytes and macrophages, lymphoma, and carcinoma cells facilitates escape from cancer immune surveillance; however, the role of KCa3.1 in IL-10 production remains unclear. The objective of the present study was to elucidate the involvement of KCa3.1 in IL-10 expression and production using the human T-cell lymphoma HuT-78 cells. In HuT-78 cells, IL-10 gene expression and production were reduced by treatment with the KCa3.1 activator, as 6-hour Western blotting showed that the protein expression ratio of phosphorylated Smad2 (P-Smad2)/ Smad2, but not P-Smad3/Smad3, was decreased by the