a2V-ATPase is the a2 isoform of vacuolar ATPase and is expressed in human trophoblast cells. a2V-ATPase resides as a 70-kDa molecule in intracellular vesicles. Upon cell stimulation, it migrates to the surface as a 50-kDa molecule, after a 20-kDa portion [N-terminus domain of the a2V-ATPase (a2NTD)] is cleaved and secreted to the extracellular environment. Previous studies showed that a2NTD-regulated cytokine production from stimulated T cells. The aim of this study was to determine if a2NTD can regulate cytokine production from immune cells that were in contact with JEG-3 cells.