title: LL37 inhibits the inflammatory endothelial response induced by viral or endogenous DNA.
abstract: In viral infection, morbidity and mortality often result from extrahepatic disease manifestations such as vasculitis. We hereby show that human microvascular endothelial cells express viral receptors of the innate immune system which are induced upon ligand engagement. Furthermore, stimulation of endothelial cells with the synthetic analog of viral DNA, poly (dA:dT), human DNA and hepatitis B virus-containing immunoprecipitates from a patient with polyarteritis nodosa induces an inflammatory response including the upregulation of adhesion molecules, which is mediated exclusively by TLR9 and involves an IRF3-dependent pathway. Thus, endothelial cells are able to actively participate in immune mediated vascular inflammation caused by viral infections. Furthermore, we provide evidence for the ability of LL37 to bind and internalize viral or endogenous DNA into non-immune cells. DNA nucleotides internalized by LL37 suppress the production of proinflammatory mediators suggesting a protective effect against direct responses to viral infection or circulating DNA-fragments of endogenous origin.
authors: Medizinische Klinik und Poliklinik IV, Innenstadt, Klinikum der Universität München, Germany.
authors: Monika
authors: M
authors: Merkle
authors: Walter Brendel Centre of Experimental Medicine and Munich Heart Alliance, Ludwig Maximilians University München, Germany; Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Germany.
authors: Joachim
authors: J
authors: Pircher
authors: Walter Brendel Centre of Experimental Medicine and Munich Heart Alliance, Ludwig Maximilians University München, Germany.
authors: Hanna
authors: H
authors: Mannell
authors: Walter Brendel Centre of Experimental Medicine and Munich Heart Alliance, Ludwig Maximilians University München, Germany.
authors: Florian
authors: F
authors: Krötz
authors: Medizinische Klinik und Poliklinik IV, Innenstadt, Klinikum der Universität München, Germany.
authors: Philipp
authors: P
authors: Blüm
authors: Medizinische Klinik und Poliklinik IV, Innenstadt, Klinikum der Universität München, Germany.
authors: Thomas
authors: T
authors: Czermak
authors: Medizinische Klinik und Poliklinik IV, Innenstadt, Klinikum der Universität München, Germany.
authors: Erik
authors: E
authors: Gaitzsch
authors: Medizinische Klinik und Poliklinik IV, Innenstadt, Klinikum der Universität München, Germany.
authors: Christine
authors: C
authors: Schneider
authors: Medizinische Klinik und Poliklinik IV, Innenstadt, Klinikum der Universität München, Germany.
authors: Simone
authors: S
authors: Köppel
authors: Medizinische Klinik und Poliklinik IV, Innenstadt, Klinikum der Universität München, Germany.
authors: Andrea
authors: A
authors: Ribeiro
authors: Medizinische Klinik und Poliklinik IV, Innenstadt, Klinikum der Universität München, Germany. Electronic address: Markus.Woernle@med.uni-muenchen.de.
authors: Markus
authors: M
authors: Wörnle
mesh_terms: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D004279:DNA, Viral / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D065206:Extracellular Traps / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D050838:Interferon Regulatory Factor-3 / Q000276:immunology; D055806:Microvessels / Q000276:immunology*; D011067:Poly dA-dT / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D018925:Chemokines; D004279:DNA, Viral; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D051217:Toll-Like Receptor 9; D011067:Poly dA-dT
keywords: DNA; LL37; TLR9; Viral