title: Signalling-dependent adverse health effects of carbon nanoparticles are prevented by the compatible solute mannosylglycerate (firoin) in vitro and in vivo.
abstract: The inhalation of combustion-derived nanoparticles leads to adverse health effects in the airways. In this context the induction of membrane-coupled signalling is considered as causative for changes in tissue homeostasis and pro-inflammatory reactions. The identification of these molecular cell reactions allowed to seek for strategies which interfere with these adverse effects. In the current study, we investigated the structurally different compatible solutes mannosylglycerate (firoin) from thermophilic bacteria and ectoine from halophilic bacteria for their capability to reduce signalling pathways triggered by carbon nanoparticles in target cells in the lung. The pre-treatment of lung epithelial cells with both substances decreased the particle-specific activation of mitogen-activated protein kinases and also the endpoints proliferation and apoptosis. Firoin applied into the lungs of animals, like ectoine, led to a significant reduction of the neutrophilic lung inflammation induced by particle exposure. The pro-inflammatory effect of carbon nanoparticles on human neutrophil granulocytes ex vivo was significantly reduced by both substances via the reduction of the anti-apoptotic membrane-dependent signalling. The data of this study together with earlier studies demonstrate that two structurally non-related compatible solutes are able to prevent pathogenic reactions of the airways to carbon nanoparticles by interfering with signalling events. The findings highlight the preventive or therapeutic potential of compatible solutes for adverse health effects caused by particle exposure of the airways.
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Autengruber
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sydlik
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kroker
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Hornstein
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Ale-Agha
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stöckmann
authors.affiliation: bitop AG, Witten, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bilstein
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Catrin
authors.initials: C
authors.lastname: Albrecht
authors.affiliation: Department of Traumatology and Hand Surgery, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Adnana
authors.initials: A
authors.lastname: Paunel-Görgülü
authors.affiliation: Department of Traumatology and Hand Surgery, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Christoph V
authors.initials: CV
authors.lastname: Suschek
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; Zentrum für Molekulare Medizin der Medizinischen Fakultät der Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Unfried
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002244:Carbon / Q000737:chemistry*; D002460:Cell Line; D004789:Enzyme Activation; D005988:Glyceric Acids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008358:Mannose / Q000031:analogs & derivatives* / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053758:Nanoparticles / Q000009:adverse effects*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D015398:Signal Transduction
chemical_list: D005988:Glyceric Acids; C402688:mannosylglycerate; D002244:Carbon; D020928:Mitogen-Activated Protein Kinases; D008358:Mannose