Figure 5.

Putative signaling for pannexin-1/ATP/P2X₇-dependent and -independent release of IL-1β by TLR2 and TLR4 agonists, respectively. IL-1β release was induced by TLR2 and TLR4 ligands from human monocytes. A) TLR2 agonists induce expression of pro-IL-1β via NF-κB and activate ATP release via panexin-1. ATP activates P2X₇, which mediates potassium ion efflux and hyperpolarization, leading to activation of caspase-1, which cleaves pro-Il-1β, resulting in release of mature IL-1β. B) TLR4 agonist LPS activates TLR4 and NF-κB pathways, resulting in increased expression of pro-IL-1β. LPS evades pannexin-1 activation resulting in reduced ATP release, but activates MaxiK channels resulting in potassium ion efflux and hyperpolarization, and thus resulting in release of mature IL-1β.