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Here we show that interleukin (IL)\u201018, a proinflammatory and pro\u2010hypertrophic cytokine, stimulates FN expression in adult human cardiac fibroblasts (HCF), an effect blocked by either the IL\u201018BP:Fc chimera or IL\u201018 neutralizing antibodies. IL\u201018 stimulated FN promoter\u2013reporter activity in HCF, a response attenuated by mutation of an NF\u2010\u03baB binding site in the FN promoter. Overexpression of p65 stimulated FN transcription. IL\u201018 stimulated in vitro (p65, p50) and in vivo NF\u2010\u03baB DNA binding activities, and induced \u03baB\u2010dependent reporter gene activity. These effects were inhibited by adenoviral transduction of dominant negative (dn) p65 (Ad.dnp65) and dnIKK2 (Ad.dnIKK2). Investigation of signaling intermediates revealed that IL\u201018 stimulated PI3 kinase activity (blocked by wortmannin, LY294002, or Ad.dnPI3Kp85), and Akt phosphorylation and kinase activity (blocked by SH\u20105 or Ad.dnAkt). Furthermore, targeting MyD88, IRAK1, TRAF6, PI3K, Akt, and NF\u2010\u03baB by RNA interference or dn expression vectors blunted IL\u201018 mediated FN transcription and mRNA expression. Conversely, FN stimulated IL\u201018 expression. These data provide the first evidence that IL\u201018 and FN stimulate each other's expression in HCF, and suggest a role for IL\u201018, FN and their crosstalk in myocardial hypertrophy and remodeling, disease states characterized by enhanced FN expression and fibrosis. J. Cell. Physiol. 215: 697\u2013707, 2008. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21348","type":"journal-article","created":{"date-parts":[[2007,12,6]],"date-time":"2007-12-06T20:47:58Z","timestamp":1196974078000},"page":"697-707","source":"Crossref","is-referenced-by-count":64,"title":["Interleukin\u201018 stimulates fibronectin expression in primary human cardiac fibroblasts via PI3K\u2010Akt\u2010dependent NF\u2010\u03baB activation"],"prefix":"10.1002","volume":"215","author":[{"given":"Venkatapuram Seenu","family":"Reddy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf Egan","family":"Harskamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margreet Willie","family":"van 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