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Although secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) is essential for the elimination of invading<jats:italic>Legionella<\/jats:italic>spp., mechanisms of<jats:italic>Legionella pneumophila<\/jats:italic>-induced release of this cytokine are widely unknown.<\/jats:p><jats:p>In this study, we have demonstrated a toll-like receptor (TLR)2- and TLR5-dependent release of GM-CSF in<jats:italic>L. pneumophila<\/jats:italic>-infected human alveolar epithelial cells. GM-CSF secretion was not dependent on the bacteria type II or type IV secretion system. Furthermore, an increase in protein kinase C (PKC) activity, particularly PKC\u03b1 and PKC\u03f5, was noted. Blocking of PKC\u03b1 and PKC\u03f5 activity or expression, but not of PKC\u03b2, PKC\u03b4, PKC\u03b7, PKC<jats:italic>\u03b8<\/jats:italic>, and PKC\u03b6, significantly reduced the synthesis of GM-CSF in infected cells. While PKC\u03b1 was critical for the initiation of a nuclear factor-\u03baB-mediated GM-CSF expression, PKC\u03f5 regulated GM-CSF production<jats:italic>via<\/jats:italic>activator protein 1.<\/jats:p><jats:p>Thus, differential regulation of GM-CSF, production by PKC isoforms, contributes to the host response in Legionnaires' disease.<\/jats:p>","DOI":"10.1183\/09031936.00171908","type":"journal-article","created":{"date-parts":[[2009,3,27]],"date-time":"2009-03-27T00:45:36Z","timestamp":1238114736000},"page":"1171-1179","source":"Crossref","is-referenced-by-count":7,"title":["PKC\u03b1 and PKC\u03f5 differentially regulate<i>Legionella pneumophila<\/i>-induced GM-CSF"],"prefix":"10.1183","volume":"34","author":[{"given":"K.","family":"Vardarova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Scharf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Lang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Schmeck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Opitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Eitel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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