• P2X7 receptor activation leads to NLRP3-independent IL-1β release by human macrophages.

P2X7 receptor activation leads to NLRP3-independent IL-1β release by human macrophages.

Cell communication and signaling : CCS (2023-11-24)
Judith Bockstiegel, Jonas Engelhardt, Günther Weindl

The purinergic receptor P2X7 plays a crucial role in infection, inflammation, and cell death. It is thought that P2X7 receptor stimulation triggers processing and release of the pro-inflammatory cytokine interleukin (IL)-1β by activation of the NLRP3 inflammasome; however, the underlying mechanisms remain poorly understood. Modulation of IL-1β secretion was studied in THP-1 macrophages. Adenosine 5'-triphosphate (ATP), BzATP, nigericin and pharmacological inhibitors of P2X receptors, inflammatory caspases and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome were used to characterize signaling. In primed macrophages, IL-1β release was increased after P2X7 receptor activation by ATP and 2,3-O-(4-benzoylbenzoyl)-ATP (BzATP). Pharmacological inhibition or genetic knockout of NLRP3 does not completely inhibit IL-1β release in TLR2/1-primed macrophages. Increase in extracellular K+ as well as inhibition of caspase-1 or serine proteases maintained IL-1β release in macrophages stimulated with P2X7 receptor agonists at 50%. Our findings suggest a previously unrecognized mechanism of P2X7 receptor mediated IL-1β release and highlight the existence of an NLRP3-independent pathway in human macrophages. Video Abstract.

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Product Description

E-64 Protease Inhibitor, The E-64 Protease Inhibitor, also referenced under CAS 66701-25-5, controls the biological activity of E-64 Protease. This small molecule/inhibitor is primarily used for Protease Inhibitors applications.
Bay 11-7082, ≥98% (HPLC), powder