Cyclooxygenase-2 activity regulates recruitment of VEGF-secreting Ly6Chigh monocytes in ventilator-induced lung injury

Tzu Hsiung Huang, Pin-Hui Fang, Jhy Ming Li, Huan Yuan Ling, Chieh Mo Lin, Chung Sheng Shi

Research output: Contribution to journalArticle

Abstract

Mechanical ventilation is usually required for saving lives in critically ill patients; however, it can cause ventilator-induced lung injury (VILI). As VEGF-secreting Ly6Chigh monocytes are involved in VILI pathogenesis, we investigated whether cyclooxygenase-2 (COX-2) activity regulates the recruitment of VEGF-secreting Ly6Chigh monocytes during VILI. The clinically relevant two-hit mouse model of VILI, which involves the intravenous injection of lipopolysaccharide prior to high tidal volume (HTV)-mechanical ventilation, was used in this study. To investigate the role of COX-2 in the recruitment of VEGF-secreting Ly6Chigh monocytes during VILI, celecoxib, which is a clinical COX-2 inhibitor, was administered 1 h prior to HTV-mechanical ventilation. Pulmonary vascular permeability and leakage, inflammatory leukocyte infiltration, and lung oxygenation levels were measured to assess the severity of VILI. HTV-mechanical ventilation significantly increased the recruitment of COX-2-expressing Ly6Chigh, but not Ly6Clow, monocytes. Celecoxib significantly diminished the recruitment of Ly6Chigh monocytes, attenuated the levels of VEGF and total protein in bronchoalveolar lavage fluid, and restored pulmonary oxygenation during VILI. Our findings demonstrate that COX-2 activity is important in the recruitment of VEGF-secreting Ly6Chigh monocytes, which are involved in VILI pathogenesis, and indicate that the suppression of COX-2 activity might be a useful strategy in mitigating VILI.

Original languageEnglish
Article number1771
JournalInternational journal of molecular sciences
Volume20
Issue number7
DOIs
Publication statusPublished - 2019 Apr 1

Fingerprint

ventilators
Ventilator-Induced Lung Injury
Personnel Selection
monocytes
Cyclooxygenase 2
lungs
Vascular Endothelial Growth Factor A
Celecoxib
Monocytes
Oxygenation
ventilation
Artificial Respiration
Tidal Volume
pathogenesis
Cyclooxygenase 2 Inhibitors
oxygenation
Lung
Infiltration
Lipopolysaccharides
Prostaglandin-Endoperoxide Synthases

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Huang, Tzu Hsiung ; Fang, Pin-Hui ; Li, Jhy Ming ; Ling, Huan Yuan ; Lin, Chieh Mo ; Shi, Chung Sheng. / Cyclooxygenase-2 activity regulates recruitment of VEGF-secreting Ly6Chigh monocytes in ventilator-induced lung injury. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 7.
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Cyclooxygenase-2 activity regulates recruitment of VEGF-secreting Ly6Chigh monocytes in ventilator-induced lung injury. / Huang, Tzu Hsiung; Fang, Pin-Hui; Li, Jhy Ming; Ling, Huan Yuan; Lin, Chieh Mo; Shi, Chung Sheng.

In: International journal of molecular sciences, Vol. 20, No. 7, 1771, 01.04.2019.

Research output: Contribution to journalArticle

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T1 - Cyclooxygenase-2 activity regulates recruitment of VEGF-secreting Ly6Chigh monocytes in ventilator-induced lung injury

AU - Huang, Tzu Hsiung

AU - Fang, Pin-Hui

AU - Li, Jhy Ming

AU - Ling, Huan Yuan

AU - Lin, Chieh Mo

AU - Shi, Chung Sheng

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AB - Mechanical ventilation is usually required for saving lives in critically ill patients; however, it can cause ventilator-induced lung injury (VILI). As VEGF-secreting Ly6Chigh monocytes are involved in VILI pathogenesis, we investigated whether cyclooxygenase-2 (COX-2) activity regulates the recruitment of VEGF-secreting Ly6Chigh monocytes during VILI. The clinically relevant two-hit mouse model of VILI, which involves the intravenous injection of lipopolysaccharide prior to high tidal volume (HTV)-mechanical ventilation, was used in this study. To investigate the role of COX-2 in the recruitment of VEGF-secreting Ly6Chigh monocytes during VILI, celecoxib, which is a clinical COX-2 inhibitor, was administered 1 h prior to HTV-mechanical ventilation. Pulmonary vascular permeability and leakage, inflammatory leukocyte infiltration, and lung oxygenation levels were measured to assess the severity of VILI. HTV-mechanical ventilation significantly increased the recruitment of COX-2-expressing Ly6Chigh, but not Ly6Clow, monocytes. Celecoxib significantly diminished the recruitment of Ly6Chigh monocytes, attenuated the levels of VEGF and total protein in bronchoalveolar lavage fluid, and restored pulmonary oxygenation during VILI. Our findings demonstrate that COX-2 activity is important in the recruitment of VEGF-secreting Ly6Chigh monocytes, which are involved in VILI pathogenesis, and indicate that the suppression of COX-2 activity might be a useful strategy in mitigating VILI.

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