Mechanistic Inhibition of IL-1β with a Focus on the P2X7 Receptor

Abstract

Inflammatory mediators are important molecules that adjust the inflammatory response and prevent tissue damage. Cytokines are relevant mediators involved in inflammation. The interleukin-1 (IL-1) family is a well-known cytokine group that regulates inflammatory responses, in which IL-1β plays a pivotal role in the promotion of inflammation. Although there are several underlying mechanisms, the nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) pathway is the most studied pathway for the secretion of IL-1β. The NLRP3 inflammasome is a protein complex formed after extracellular adenosine triphosphate (eATP) binds to the P2X family purinergic receptor 7 (P2X7R), and NLRP3 inflammasome activation results in IL-1β release. The P2X7 receptor plays a crucial role in the immune response, and its modulation may trigger the development of pathological conditions characterized by inflammation. Therefore, it is important to highlight the P2X7 receptor as a potential therapeutic target in diseases in which an inflammatory profile is observed due to high concentrations of secreted IL-1β. This study aimed to elucidate the mechanism by which the P2X7 receptor may affect IL-1β cytokine release.