The purinergic P2x7 receptor is expressed on monocytes in Behcet's disease and is modulated by TNF-alpha.

The P2x7 receptor (P2x7r) is expressed in innate immune cells (e.g. monocyte/macrophages), playing a key role in IL-1beta release. Since innate immune activation and IL-1beta release seem to be implicated in Behcet's disease (BD), a systemic immune-inflammatory disorder of unknown origin, we hypothesized that P2x7r 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 P2x7r expression and Ca(2+) permeability induced by the selective P2x7r agonist 2'-3'-O-(4-benzoylbenzoyl)ATP (BzATP) was observed. Moreover, IL-1beta release from LPS-primed monocytes stimulated with BzATP was markedly higher in BD patients than in controls. TNF-alpha-incubated monocytes from healthy subjects almost reproduced the findings observed in BD patients, as demonstrated by the increase in P2x7r expression and BzATP-induced Ca(2+) intake. Our results provide evidence that in BD monocytes both the expression and function of the P2x7r are increased compared with healthy controls, as the possible result, at least in part, of a positive modulating effect of TNF-alpha on the receptor. These data indicate P2x7r as a new potential therapeutic target for the control of BD, further supporting the rationale for the use of anti-TNF-alpha drugs in the treatment of the disease.