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Acute gout was induced by injection of monosodium urate (MSU) crystals into the tibiofemoral joint of mice. The involvement of PI3K\u03b3 was evaluated using a selective inhibitor and mice deficient for PI3K\u03b3 (PI3K\u03b3\u2212\/\u2212) or with loss of kinase activity. Neutrophils recovered from the inflamed joint were quantified and stained for phosphorylated Akt (pAkt) and production of reactive oxygen species (ROS). The adherence of leukocytes to the joint microvasculature was assessed by intravital microscopy and cleaved caspase-1 by Western blot. Injection of MSU crystals induced massive accumulation of neutrophils expressing phosphorylated Akt. In the absence of PI3K\u03b3, there was reduction of pAkt expression, chemokine production, and neutrophil recruitment. Genetic or pharmacological inhibition of PI3K\u03b3 reduced the adherence of leukocytes to the joint microvasculature, even in joints with established inflammation. Neutrophils from PI3K\u03b3\u2212\/\u2212 mice produced less ROS than wild-type neutrophils. There was decreased joint damage and dysfunction in the absence of PI3K\u03b3. In addition, in the absence of PI3K\u03b3 activity, there was reduction of cleaved caspase-1 and IL-1\u03b2 production in synovial tissue after injection of MSU crystals and leukotriene B4. Our studies suggest that PI3K\u03b3 is crucial for MSU crystal\u2013induced acute joint inflammation. It is necessary for regulating caspase-1 activation and for mediating neutrophil migration and activation. Drugs that impair PI3K\u03b3 function may be useful to control acute gout inflammation.<\/jats:p>","DOI":"10.1002\/jlb.ma1118-470rr","type":"journal-article","created":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T08:50:03Z","timestamp":1565254203000},"page":"619-629","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Phosphoinositide-3 kinase gamma regulates caspase-1 activation and leukocyte recruitment in acute murine gout"],"prefix":"10.1093","volume":"106","author":[{"given":"L\u00edvia D","family":"Tavares","sequence":"first","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Galv\u00e3o","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian V","family":"Costa","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia V","family":"Batista","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia C R","family":"Rossi","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila B","family":"Brito","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alesandra C","family":"Reis","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso M","family":"Queiroz-Junior","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda D","family":"Braga","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda M","family":"Coelho","sequence":"additional","affiliation":[{"name":"Vollum Institute, Oregon Health and Science University , Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C","family":"Dias","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario S","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of S\u00e3o Paulo FMRP\/USP , Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Pinho","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro M","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo 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