title: Mitochondrial DNA and TLR9 Signaling Is Not Involved in Mechanical Ventilation-Induced Inflammation.
abstract: Exogenous administration of mitochondrial DNA (mtDNA) causes inflammatory lung injury in a toll-like receptor (TLR) 9-dependent manner. We investigated whether mechanical ventilation results in endogenous release of mtDNA and whether TLR9 plays a role in the pulmonary inflammatory response induced by mechanical ventilation.Wild-type and TLR9/ C57bl/6 mice were ventilated with low (8 mL/kg) and high (32 mL/kg) tidal volumes for 4 hours. Levels of nuclear DNA and mtDNA in bronchoalveolar lavage fluid, as well as pulmonary concentrations of keratinocyte-derived chemokine, interleukin-1β, and interleukin-6, were determined.Cytokine and nuclear DNA, but not mtDNA, levels were increased after mechanical ventilation with both tidal volumes. Cytokine concentrations were similar between wild-type and TLR9/ mice. Mechanical ventilation does not result in the release of mtDNA, and TLR9 is not involved in mechanical ventilation-induced inflammation.
authors.affiliation: From the Departments of *Anesthesiology and †Intensive Care Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands; and ‡Radboud Centre for Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Timmermans
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kox
authors.forename: Michiel
authors.initials: M
authors.lastname: Vaneker
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Scheffer
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D018925:Chemokines; D004272:DNA, Mitochondrial / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012121:Respiration, Artificial; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D055397:Ventilator-Induced Lung Injury / Q000503:physiopathology*
chemical_list: D018925:Chemokines; D004272:DNA, Mitochondrial; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; C577686:interleukin-6, mouse; C074302:keratinocyte-derived chemokines