The purinergic P2×7 receptor is expressed on monocytes in Behçet's disease and is modulated by TNF-α

Abstract

The P2×7 receptor (P2×7r) is expressed in innate immune cells (e.g. monocyte/macrophages), playing a key role in IL-1β release. Since innate immune activation and IL-1β release seem to be implicated in Behçet's disease (BD), a systemic immune-inflammatory disorder of unknown origin, we hypothesized that P2×7r is involved in the pathogenesis of the disease. Monocytes were isolated from 18 BD patients and 17 healthy matched controls. In BD monocytes, an increased P2×7r expression and Ca2+ permeability induced by the selective P2×7r agonist 2′-3′-O-(4-benzoylbenzoyl)ATP (BzATP) was observed. Moreover, IL-1β release from LPS-primed monocytes stimulated with BzATP was markedly higher in BD patients than in controls. TNF-α-incubated monocytes from healthy subjects almost reproduced the findings observed in BD patients, as demonstrated by the increase in P2×7r expression and BzATP-induced Ca2+ intake. Our results provide evidence that in BD monocytes both the expression and function of the P2×7r are increased compared with healthy controls, as the possible result, at least in part, of a positive modulating effect of TNF-α on the receptor. These data indicate P2×7r as a new potential therapeutic target for the control of BD, further supporting the rationale for the use of anti-TNF-α drugs in the treatment of the disease. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.