Fig. 5

Proposed mechanism for NLRP3-independent IL-1β release by human macrophages after P2X7 receptor activation. Activation of TLR2/1 by Pam₃CSK₄ leads to NF-κB mediated production of pro-IL-1β and components of NLRP3 inflammasome. Nigericin-mediated K⁺ efflux leads to NLRP3 inflammasome oligomerization causing serine protease- and caspase-dependent IL-1β release. In contrast, P2X7 receptor stimulation by BzATP potentially initiates two distinct IL-1β releasing mechanisms that are both NLRP3-independent. One mechanism relies on K⁺ efflux and requires activation of caspase-1 and serine proteases. The other mechanism is independent of K⁺ efflux, caspases, and serine-, cysteine-, and aspartic proteases, suggesting the involvement of other mechanisms for proteolytic processing of IL-1β