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 lipopolysaccharide-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.

Castrichini, M., Lazzerini, P.E., Gamberucci, A., Capecchi, P.L., Franceschini, R., Natale, M., et al. (2014). The purinergic P2×7 receptor is expressed on monocytes in Behçet's disease and is modulated by TNF-α. EUROPEAN JOURNAL OF IMMUNOLOGY, 44(1), 227-238 [10.1002/eji.201343353].

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

Castrichini, Monica;Lazzerini, Pietro Enea;Gamberucci, Alessandra;Capecchi, Pier Leopoldo;Franceschini, Rossella;Natale, Mariarita;Moramarco, Antonio;Zimbone, Stefania;Gianchecchi, Elena;Montilli, Cinzia;Cantarini, Luca;Galeazzi, Mauro;Laghi-Pasini, Franco
2014-01-01

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 lipopolysaccharide-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.
2014
Castrichini, M., Lazzerini, P.E., Gamberucci, A., Capecchi, P.L., Franceschini, R., Natale, M., et al. (2014). The purinergic P2×7 receptor is expressed on monocytes in Behçet's disease and is modulated by TNF-α. EUROPEAN JOURNAL OF IMMUNOLOGY, 44(1), 227-238 [10.1002/eji.201343353].
File in questo prodotto:
File Dimensione Formato  
Purinergic-P2x7-2014.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 909.05 kB
Formato Adobe PDF
909.05 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/45903
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo