PT - JOURNAL ARTICLE AU - K. Vardarova AU - S. Scharf AU - F. Lang AU - B. Schmeck AU - B. Opitz AU - J. Eitel AU - A. C. Hocke AU - H. Slevogt AU - A. Flieger AU - S. Hippenstiel AU - N. Suttorp AU - P. D. N'Guessan TI - PKCα and PKCϵ differentially regulate <em>Legionella pneumophila</em>-induced GM-CSF AID - 10.1183/09031936.00171908 DP - 2009 Nov 01 TA - European Respiratory Journal PG - 1171--1179 VI - 34 IP - 5 4099 - http://erj.ersjournals.com/content/34/5/1171.short 4100 - http://erj.ersjournals.com/content/34/5/1171.full SO - Eur Respir J2009 Nov 01; 34 AB - Legionella pneumophila is an important causative agent of severe pneumonia in humans. The human alveolar epithelium is an effective barrier for inhaled microorganisms and actively participates in the initiation of innate host defense. Although secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) is essential for the elimination of invading Legionella spp., mechanisms of Legionella pneumophila-induced release of this cytokine are widely unknown. In this study, we have demonstrated a toll-like receptor (TLR)2- and TLR5-dependent release of GM-CSF in L. pneumophila-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 PKCα and PKCϵ, was noted. Blocking of PKCα and PKCϵ activity or expression, but not of PKCβ, PKCδ, PKCη, PKCθ, and PKCζ, significantly reduced the synthesis of GM-CSF in infected cells. While PKCα was critical for the initiation of a nuclear factor-κB-mediated GM-CSF expression, PKCϵ regulated GM-CSF production via activator protein 1. Thus, differential regulation of GM-CSF, production by PKC isoforms, contributes to the host response in Legionnaires' disease.