Figure 1.

Nucleotide-binding oligomerization domain-like receptors family pyrin domain containing 3 (NLRP3) inflammasome activation and characterization of various pharmacological inhibitors of the NLRP3 inflammasome signaling cascade. Effective activation of the NLRP3 inflammasome requires a priming signal prior to or coincident with a secondary NLRP3-specific activating signal. First, NLRP3 inflammasome priming or initiating is accomplished by nuclear factor kappa B (NF-κB)-activating receptors including Toll-like receptors (TLRs), interleukin (IL)-1 receptor, tumor necrosis factor receptor, and the cytosolic pattern recognition receptor nucleotide-binding oligomerization domain 2 (signal I). Subsequently, the second signaling is provided by one of various agonists that triggers NLRP3-specific activation, assembling of the NLRP3 inflammasome complex, and ultimately culminates in the activation of casp1 as well as the secretion of mature IL-1β and IL-18 (signal II). So far, a variety of triggers with different properties have been shown for NLRP3 inflammasome activation. The diverse group of activators includes crystals and particles such as alum, silica, asbestos, monosodium urate that requires phagocytosis for activation, adenosine triphosphate (ATP) acting via its cell surface purinergic P2X7 receptor (ROS), and pore-forming toxins such as nigericin.