title: 1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro.
abstract: We have previously demonstrated the nucleic acid binding capacity of phenanthridine derivatives (PHTs). Because nucleic acids are potent inducers of innate immune response through Toll-like receptors (TLRs), and because PTHs bear a structural resemblance to commonly used synthetic ligands for TLR7/8, we hypothesized that PHTs could modulate/activate immune response. We found that compound M199 induces secretion of IL-6, IL-8 and TNFα in human PBMCs and inhibits TLR3/9 activation in different cellular systems (PBMCs, HEK293 and THP-1 cell lines).
authors.affiliation: Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Natalija Knežević
authors.initials: NK
authors.lastname: Teofilović
authors.affiliation: Biontech AG, Mainz, Germany.
authors.forename: Mahjoub
authors.initials: M
authors.lastname: Bihi
authors.affiliation: Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Marijana Radić
authors.initials: MR
authors.lastname: Stojković
authors.affiliation: Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Lidija M
authors.initials: LM
authors.lastname: Tumir
authors.affiliation: Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Katja
authors.initials: K
authors.lastname: Ester
authors.affiliation: Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Marijeta
authors.initials: M
authors.lastname: Kralj
authors.affiliation: Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Dragomira
authors.initials: D
authors.lastname: Majhen
authors.affiliation: Faculty of Natural Science, Zagreb, Croatia.
authors.forename: Nada
authors.initials: N
authors.lastname: Oršolić
authors.affiliation: Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Lepur
authors.affiliation: Department of Medical Oncology, University Hospital Center Zagreb, Croatia.
authors.forename: Damir
authors.initials: D
authors.lastname: Vrbanec
authors.affiliation: University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb, Croatia.
authors.forename: Alemka
authors.initials: A
authors.lastname: Markotić
authors.affiliation: Department of Oral Biology, Faculty of Dentistry, University of Oslo, Norway.
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Dembić
authors.affiliation: University of Tübingen, Department of Immunology, Germany.
authors.forename: Alexander N R
authors.initials: AN
authors.lastname: Weber
authors.affiliation: Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Piantanida
authors.affiliation: Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Oliver
authors.initials: O
authors.lastname: Vugrek
authors.affiliation: TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University GmbH, Mainz, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Diken
authors.affiliation: Ruđer Bošković Institute, Zagreb, Croatia. Electronic address: jknezev@irb.hr.
authors.forename: Jelena
authors.initials: J
authors.lastname: Knežević
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007364:Intercalating Agents / Q000494:pharmacology; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism* / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: C000621523:1-ethyl-3-(6-methylphenanthridine-8-yl)urea; C508606:CXCL8 protein, human; C526902:CpG ODN 2216; C508600:IL6 protein, human; D007155:Immunologic Factors; D007364:Intercalating Agents; D016898:Interferon-alpha; D015850:Interleukin-6; D016209:Interleukin-8; C000615642:ODN2006; D009838:Oligodeoxyribonucleotides; D010617:Phenanthridines; C495344:TLR3 protein, human; C495371:TLR9 protein, human; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D014508:Urea
keywords: Cytokines; Immunomodulation; PBMCs; Phenanthridines; TLR