title: Mechanical ventilation induces a Toll/interleukin-1 receptor domain-containing adapter-inducing interferon beta-dependent inflammatory response in healthy mice.
abstract: BACKGROUND
  Mechanical ventilation (MV) can induce lung injury. Proinflammatory cytokines have been shown to play an important role in the development of ventilator-induced lung injury. Previously, the authors have shown a role for Toll-like receptor 4 signaling. The current study aims to investigate the role of Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-beta (TRIF), a protein downstream of Toll-like receptors, in the development of the inflammatory response after MV in healthy mice.
  
  
  METHODS
  Wild-type C57BL6 and TRIF mutant mice were mechanically ventilated for 4 h. Lung tissue and plasma was used to investigate changes in cytokine profile, leukocyte influx, and nuclear factor-kappaB activity. In addition, experiments were performed to assess the role of TRIF in changes in cardiopulmonary physiology after MV.
  
  
  RESULTS
  MV significantly increased messenger RNA expression of interleukin (IL)-1beta in wild-type mice, but not in TRIF mutant mice. In lung homogenates, MV increased levels of IL-1alpha, IL-1beta, and keratinocyte-derived chemokine in wild-type mice. In contrast, in TRIF mutant mice, only a minor increase in IL-1beta and keratinocyte-derived chemokine was found after MV. Nuclear factor-kappaB activity after MV was significantly lower in TRIF mutant mice compared with wild-type mice. In plasma, MV increased levels of IL-6 and keratinocyte-derived chemokine. In TRIF mutant mice, no increase of IL-6 was found after MV, and the increase in keratinocyte-derived chemokine appeared less pronounced. TRIF deletion did not affect cardiopulmonary physiology after MV.
  
  
  CONCLUSIONS
  The current study supports a prominent role for TRIF in the development of the pulmonary and systemic inflammatory response after MV.
authors.affiliation: Department of Anesthesiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.vaneker@anes.umcn.nl
authors.forename: Michiel
authors.initials: M
authors.lastname: Vaneker
authors.forename: Leo M A
authors.initials: LM
authors.lastname: Heunks
authors.forename: Leo A
authors.initials: LA
authors.lastname: Joosten
authors.forename: Hieronymus W H
authors.initials: HW
authors.lastname: van Hees
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Snijdelaar
authors.forename: Feico J
authors.initials: FJ
authors.lastname: Halbertsma
authors.forename: Jan
authors.initials: J
authors.lastname: van Egmond
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Johannes G
authors.initials: JG
authors.lastname: van der Hoeven
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Scheffer
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D009841:Oligonucleotides / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012121:Respiration, Artificial; D055397:Ventilator-Induced Lung Injury / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009841:Oligonucleotides; D012333:RNA, Messenger; C476286:Ticam1 protein, mouse