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Mitochondrial DNA and TLR9 Signaling Is Not Involved in Mechanical Ventilation-Induced Inflammation

Kim Timmermans1, Matthijs Kox, Michiel Vaneker

  • 1From 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.

Anesthesia and Analgesia
|January 19, 2017
PubMed

Insights

Mechanical ventilation increases lung inflammation and nuclear DNA release, but not mitochondrial DNA (mtDNA). The toll-like receptor (TLR) 9 pathway is not involved in this inflammation, contrary to expectations based on exogenous mtDNA studies.

Area of Science:

  • Immunology
  • Pulmonary Medicine
  • Molecular Biology

Background:

  • Mitochondrial DNA (mtDNA) can trigger inflammatory lung injury via toll-like receptor (TLR) 9.
  • The role of endogenous mtDNA release and TLR9 in mechanical ventilation-induced lung inflammation is unclear.

Purpose of the Study:

  • To investigate if mechanical ventilation causes endogenous release of mtDNA.
  • To determine if TLR9 mediates pulmonary inflammation during mechanical ventilation.

Main Methods:

  • Wild-type and TLR9 knockout mice were subjected to low or high tidal volume mechanical ventilation for 4 hours.
  • Levels of nuclear DNA and mtDNA in bronchoalveolar lavage fluid were measured.
  • Pulmonary inflammatory markers (cytokines) were quantified.

Main Results:

  • Mechanical ventilation increased levels of nuclear DNA and cytokines in bronchoalveolar lavage fluid.
  • Mitochondrial DNA (mtDNA) levels did not increase after mechanical ventilation.
  • Cytokine levels were similar in wild-type and TLR9 knockout mice, indicating no TLR9 involvement.

Conclusions:

  • Mechanical ventilation does not lead to endogenous release of mtDNA into the lungs.
  • Toll-like receptor 9 (TLR9) does not play a role in the pulmonary inflammatory response induced by mechanical ventilation.

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