The N-terminus Domain of the a2 Isoform of Vacuolar ATPase Can Regulate Interleukin-1β Production from Mononuclear Cells in Co-culture with JEG-3 Choriocarcinoma Cells

Problem 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. Method of study Peripheral blood mononuclear cells (PBMC) from females were co‐cultured with JEG‐3 cells in the presence or absence of a2NTD, and supernatants were analyzed by enzyme‐linked immunosorbent assay for interleukin (IL)‐1β. Additionally, PBMC cultured with JEG‐3 cells, in the presence or absence of a2NTD, were analyzed for cytokine gene expression by gene arrays. Results There was an increased secretion of IL‐1β and a decrease in type I and II IL‐1 receptors (IL1RA and IL‐1R2) gene expression in PBMC that were co‐cultured with JEG‐3 cells in the presence of a2NTD. Conclusion These data suggest a role for a2NTD in the regulation of IL‐1β pro‐inflammatory cytokine production at the fetal–maternal interface.