The purinergic P2×7 receptor is expressed on monocytes in Behçet's disease and is modulated by TNF-α.
Eur J Immunol
; 44(1): 227-38, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24105615
ABSTRACT
The P2×7 receptor (P2×7r) is expressed in innate immune cells (e.g. monocyte/macrophages), playing a key role in IL-1ß release. Since innate immune activation and IL-1ß 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 Ca(2+) permeability induced by the selective P2×7r agonist 2'-3'-O-(4-benzoylbenzoyl)ATP (BzATP) was observed. Moreover, IL-1ß 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 Ca(2+) 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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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Monócitos
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Síndrome de Behçet
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Fator de Necrose Tumoral alfa
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Interleucina-1beta
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Receptores Purinérgicos P2X7
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Itália