Regulation of P2X7 receptor expression is of interest because activation of this receptor by extracellular ATP triggers maturation and release of the pro-inflammatory cytokine interleukin-1β (IL-1β) in monocytes and macrophages. We report that interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) synergistically induce P2X7R mRNA and functional responses in the human THP-1 monocytic cell line. Induction was dose dependent, with maximal functional activity requiring 1000 units/mL IFN-γ and 10 ng/mL TNF-α and incubations of 36-72 h. The up-regulation of P2X7R function by lipopolysaccharide (LPS)/IFN-γ and TNF-α/IFN-γ was markedly attenuated by coincubation with prostaglandin E2 or the cell permeant cyclic AMP analog dibutyryl cAMP (Bt2cAMP). Bt2cAMP did not significantly alter P2X7 function in HEK-293 cells stably transfected with the human P2X7 cDNA, indicating that Bt2cAMP does not exert a generalized effect on P2X7R synthesis or downstream signal transduction. These studies demonstrate that elevated cAMP negatively modulates P2X7R expression.
- Cellular activation