The purinergic P2×7 receptor is expressed on monocytes in Behçet's disease and is modulated by TNF‐α |
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Authors: | Monica Castrichini Pietro Enea Lazzerini Alessandra Gamberucci Pier Leopoldo Capecchi Rossella Franceschini Mariarita Natale Mohamed Hammoud Antonio Moramarco Stefania Zimbone Elena Gianchecchi Cinzia Montilli Gianluca Ricci Enrico Selvi Luca Cantarini Mauro Galeazzi Franco Laghi‐Pasini |
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Institution: | 1. Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy;2. Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy |
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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. |
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Keywords: | Behç et's disease IL‐1β Monocytes P2 × 7 receptor TNF‐α |
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