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NADPH oxidase NOX2 mediates TLR2/6-dependent release of GM-CSF from endothelial cells.
Schuett, Jutta; Schuett, Harald; Oberoi, Raghav; Koch, Ann-Kathrin; Pretzer, Silke; Luchtefeld, Maren; Schieffer, Bernhard; Grote, Karsten.
Afiliação
  • Schuett J; Department of Cardiology and Angiology, Philipps-University, Marburg, Germany.
  • Schuett H; Department of Cardiology and Angiology, Philipps-University, Marburg, Germany.
  • Oberoi R; Department of Cardiology and Angiology, Philipps-University, Marburg, Germany.
  • Koch AK; Department of Cardiology and Angiology, Philipps-University, Marburg, Germany.
  • Pretzer S; Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
  • Luchtefeld M; Department of Cardiology and Angiology, Philipps-University, Marburg, Germany.
  • Schieffer B; Department of Cardiology and Angiology, Philipps-University, Marburg, Germany.
  • Grote K; Department of Cardiology and Angiology, Philipps-University, Marburg, Germany; karsten.grote@staff.uni-marburg.de.
FASEB J ; 31(6): 2612-2624, 2017 06.
Article em En | MEDLINE | ID: mdl-28274989
NADPH oxidase-generated reactive oxygen species (ROS) from immune cells are well known to be important for pathogen killing in response to TLR ligands. Here, we investigated a new aspect of NADPH oxidase in the TLR2/6-induced release of the immunologically relevant GM-CSF by endothelial cells. Stimulation of human endothelial cells with TLR2/6 agonist, MALP-2 (macrophage-activating lipopeptide of 2 kDa), induced NADPH oxidase activation and ROS formation. Inhibition by ROS scavengers and NADPH oxidase inhibitors blocked MALP-2-induced GM-CSF release. NADPH oxidase activators or ROS donors alone did not result in GM-CSF secretion; however, additional superoxide supply augmented MALP-2-induced GM-CSF secretion and restored GM-CSF levels after NADPH oxidase inhibition. MALP-2-dependent NF-ĸB activation was suppressed by NADPH oxidase inhibition, and inhibition of NF-κB completely blunted MALP-2-induced GM-CSF release. Vascular explants from mice that were deficient for the NADPH oxidase subunit p47 phox showed diminished intimal superoxide production and GM-CSF release after ex vivo stimulation with MALP-2. Moreover, an increase in circulating progenitor cells after MALP-2 injection was completely abolished in p47phox-knockout mice. Finally, MALP-2 stimulation increased mRNA expression of the major subunit NADPH oxidase, (Nox)2, in endothelial cells, and Nox2 inhibition prevented MALP-2-induced GM-CSF release. Our findings identify a Nox2-containing NADPH oxidase as a crucial regulator of the immunologic important growth factor GM-CSF after TLR2/6 stimulation in endothelial cells.-Schuett, J., Schuett, H., Oberoi, R., Koch, A.-K., Pretzer, S., Luchtefeld, M., Schieffer, B., Grote, K. NADPH oxidase NOX2 mediates TLR2/6-dependent release of GM-CSF from endothelial cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glicoproteínas de Membrana / Fator Estimulador de Colônias de Granulócitos e Macrófagos / NADPH Oxidases / Receptor 2 Toll-Like / Receptor 6 Toll-Like Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glicoproteínas de Membrana / Fator Estimulador de Colônias de Granulócitos e Macrófagos / NADPH Oxidases / Receptor 2 Toll-Like / Receptor 6 Toll-Like Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article