Regulation of P2X Family Receptor Expression and Trafficking in Human Monocytes by Pro-Inflammatory Mediators

At sites of microbial infection or tissue damage, monocytes/macrophages are exposed to extracellular ATP released from dying cells. Inflammasome activation of monocytes/macrophages by extracellular ATP is mediated by P2X4 and P2X7 receptors, two subtypes of ATP-gated ion channels. The regulation of the P2X4 and P2X7 receptors is of note because the activation of these receptors initiates the signaling cascade that leads to the maturation and release of the pro-inflammatory cytokine interleukin-1β (IL-1β) in human monocytes and macrophages. This study characterized the regulated expression and trafficking of the P2X4 and P2X7 receptors in the human THP-1 monocyte cell line. Results indicate that both  lipopolysaccharide (LPS) and  interferon-γ  (IFN-γ) led to the release of pro-IL-1β, and that the up-regulation of the P2X7 receptor by  LPS and  IFN-γ in the Human THP-1 monocytic cells was significantly attenuated by phorbol 12-myristate 13-acetate (PMA) differentiation while that of P2X4 appeared unaffected.