부산대학교 도서관

The P2X[sub 7] receptor, mainly expressed by immune cells, is a ionotropic receptor activated by high concentration of extracellular ATP. It is involved in several processes relevant to immunomodulation and inflammation. Among these processes, the production of extracellular interleukin-1β (IL-1β), a pro-inflammatory cytokine, plays a major role in the activation of the cytokine network. We have investigated the role of P2X[sub 7] receptor and of an associated calcium-activated potassium conductance (BK channels) in IL-1β maturation and releasing processes by Schwann cells. Lipopolysaccharide-primed Schwann cells synthesized large amounts of proIL-1β but did not release detectable amounts of pro or mature IL-1β. ATP on its own had no effect on the synthesis of pro-IL-1β, but a co-treatment with lipopolysaccharide and ATP led to the maturation and the release of IL-1β by Schwann cells. Both mechanisms were blocked by oxidized ATP. IL-1β-converting enzyme (ICE), the caspase responsible for the maturation of pro-IL-1β in IL-1β, was activated by P2X[sub 7] receptor stimulation. The specific inhibition of ICE by the caspase inhibitor Ac-Tyr-Val-Ala-Asp-aldehyde blocked the maturation of IL-1β. In searching for a link between the P2X[sub 7] receptor and the activation of ICE, we found that enhancing potassium efflux from Schwann cells upregulated the production of IL-1β, while strongly reducing potassium efflux led to opposite effects. Blocking BK channels actually modulated IL-1β release. Taken together, these results show that P2X[sub 7] receptor stimulation and associated BK channels, through the activation of ICE, leads to the maturation and the release of IL-1β by immune-challenged Schwann cells. [ABSTRACT FROM AUTHOR]