P2X7 Receptor Expression in Patients With Serositis Related to Systemic Lupus Erythematosus

Conclusion: Our data indicate reduced P2X7R expression and function in SLE patients compared with HC and, conversely, increased IL-6 signaling. The possible consequences of reduced P2X7R, mainly on cytokines network deregulation and lymphocyte proliferation, will be further investigated as well as the role of IL-6 as a possible therapeutic target especially in lupus serositis. Introduction With the first reports of Burnstock in 1970s, adenosine triphosphate (ATP) has passed from a simple molecule devoted to energy reserve, to a relevant extracellular signaling molecule able to mediate numerous physiological and pathological processes (Burnstock, 2006). Under physiological conditions ATP is poorly present in the extracellular space reaching concentrations in the order of nanomolar (nM). On the contrary, in pathological conditions ATP can behave as a danger associated molecular pattern (DAMP) being released from damaged or dying cells or from intact cells following either stimulation or mechanical or oxidative stress (Pellegatti et al., 2005; Burnstock, 2006; Giuliani et al., 2018). P2X7 receptor (P2X7R) is the most investigated and well defined receptor for extracellular ATP. P2X7R forms a homo-trimer ion channel allowing the efflux of K+ and influx of Na+ and Ca2+ after low ATP activation. After prolonged stimulation by high ATP, the receptor forms a pore that allows the passage of hydrophilic solutes of molecular weight up to 900 Da (Virginio et al., 1999). P2X7R ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research