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We investigated the effect of combination of salbutamol and <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b3 agonists on growth factor\u2010stimulated human bronchial smooth muscle cell (<jats:styled-content style=\"fixed-case\">BSMC<\/jats:styled-content>) proliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Synergism was quantified by the combination index\u2010isobologram method. Assays used here included analyses of growth inhibition, cell viability, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation, gene transcription, cell cycle and protein expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b3 gene was highly expressed in <jats:styled-content style=\"fixed-case\">BSMC<\/jats:styled-content> and the protein was identified in cell nuclei. Single\u2010agent salbutamol or <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b3 agonists prevented growth factor\u2010induced human <jats:styled-content style=\"fixed-case\">BSMC<\/jats:styled-content> proliferation within a micromolar range of concentrations through their specific receptor subtypes. Sub\u2010micromolar levels of combined salbutamol\u2010<jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b3 agonist inhibited growth by 50% at concentrations from \u223c2 to 12\u2010fold lower than those required for each drug alone, without induction of apoptosis or necrosis. Combination treatments also promoted cell cycle arrest at the <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>1\/<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content> transition phase and inhibition of <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> phosphorylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The synergistic interaction between <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b3 agonists and \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonists on airway smooth muscle cell proliferation highlights the anti\u2010remodelling potential of this combination in chronic lung diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2012.02180.x","type":"journal-article","created":{"date-parts":[[2012,8,27]],"date-time":"2012-08-27T19:24:11Z","timestamp":1346095451000},"page":"266-275","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Synergistic interaction between <scp>PPAR<\/scp> ligands and salbutamol on human bronchial smooth muscle cell proliferation"],"prefix":"10.1111","volume":"168","author":[{"given":"S","family":"Fogli","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Stefanelli","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Picchianti","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Del Re","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Mey","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Bardelli","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences School of Medicine University of Piemonte Orientale A. 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