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Since innate immune activation and IL<\/jats:styled-content>\u20101\u03b2 release seem to be implicated in B<\/jats:styled-content>eh\u00e7et's disease (BD<\/jats:styled-content>), a systemic immune\u2010inflammatory disorder of unknown origin, we hypothesized that P<\/jats:styled-content>2\u00d77r is involved in the pathogenesis of the disease. Monocytes were isolated from 18 BD<\/jats:styled-content> patients and 17 healthy matched controls. In BD<\/jats:styled-content> monocytes, an increased P<\/jats:styled-content>2\u00d77r expression and Ca2+<\/jats:sup> permeability induced by the selective P<\/jats:styled-content>2\u00d77r agonist 2\u2032\u20103\u2032\u2010O\u2010(4\u2010benzoylbenzoyl)ATP<\/jats:styled-content> (B<\/jats:styled-content>zATP<\/jats:styled-content>) was observed. Moreover, IL<\/jats:styled-content>\u20101\u03b2 release from LPS<\/jats:styled-content>\u2010primed monocytes stimulated with B<\/jats:styled-content>zATP<\/jats:styled-content> was markedly higher in BD<\/jats:styled-content> patients than in controls. TNF<\/jats:styled-content>\u2010\u03b1\u2010incubated monocytes from healthy subjects almost reproduced the findings observed in BD<\/jats:styled-content> patients, as demonstrated by the increase in P<\/jats:styled-content>2\u00d77r expression and B<\/jats:styled-content>zATP<\/jats:styled-content>\u2010induced Ca2+<\/jats:sup> intake. Our results provide evidence that in BD<\/jats:styled-content> monocytes both the expression and function of the P<\/jats:styled-content>2\u00d77r are increased compared with healthy controls, as the possible result, at least in part, of a positive modulating effect of TNF<\/jats:styled-content>\u2010\u03b1 on the receptor. These data indicate P<\/jats:styled-content>2\u00d77r as a new potential therapeutic target for the control of BD<\/jats:styled-content>, further supporting the rationale for the use of anti\u2010TNF<\/jats:styled-content>\u2010\u03b1 drugs in the treatment of the disease.<\/jats:p>","DOI":"10.1002\/eji.201343353","type":"journal-article","created":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T14:01:04Z","timestamp":1381240864000},"page":"227-238","source":"Crossref","is-referenced-by-count":23,"title":["The purinergic P<\/scp>2\u00d77 receptor is expressed on monocytes in B<\/scp>eh\u00e7et's disease and is modulated by TNF<\/scp>\u2010\u03b1"],"prefix":"10.1002","volume":"44","author":[{"given":"Monica","family":"Castrichini","sequence":"first","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro Enea","family":"Lazzerini","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Gamberucci","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Leopoldo","family":"Capecchi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Franceschini","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarita","family":"Natale","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Hammoud","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Moramarco","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Zimbone","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Gianchecchi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Montilli","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Selvi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Cantarini","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Galeazzi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Laghi\u2010Pasini","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.07.002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.05.004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30105"},{"key":"e_1_2_7_5_1","first-page":"S79","article-title":"Autoinflammatory syndromes","volume":"24","author":"Galeazzi M.","year":"2006","journal-title":"Clin. 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