Expression of purinergic receptors and modulation of P2X7 function by the inflammatory cytokine IFNγ in human epithelial cells

The cervical epithelial cell line, HeLa, is one of the oldest and most commonly used cell lines in cell biology laboratories. Although a truncated P2X7 receptor has recently been identified in HeLa cells, the expression of other purinergic receptors or the function of the P2X7 protein has not been characterized. We here show that HeLa cells express transcripts for most P2X and P2Y purinergic receptors. Treatment of cells with ATP or other P2X7 agonists does not stimulate cell death, but can induce atypical calcium fluxes and ion currents. Cervical epithelial cells represent an important target for sexually-transmitted pathogens and are commonly exposed to pro-inflammatory cytokines such as IFNγ. Stimulation of HeLa cells with IFNγ upregulates expression of P2X7 mRNA and full-length protein, modifies ATP-dependent calcium fluxes, and renders the cells sensitive to ATP-induced apoptosis, which can be blocked by a P2X7 antagonist. IFNγ treatment also increased dramatically the sensitivity of the intestinal epithelial cell line, HCT8, to ATP-induced apoptosis. Significantly, IFNγ also stimulated P2X7 expression on human intestinal tissues. Responses to other purinergic receptor ligands suggest that HeLa cells may also express functional P2Y1, P2Y2 and P2Y6 receptors, which could be relevant for modulating ion homeostasis in the cells.