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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


Kenneth Beaman, Microbiology and Immunology Department, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, N. Chicago, IL 60064, USA. E-mail:



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.


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.


These data suggest a role for a2NTD in the regulation of IL-1β pro-inflammatory cytokine production at the fetal–maternal interface.