S1P lyase inhibition prevents lung injury following high pressure-controlled mechanical ventilation in aging mice

• DOI: 10.1016/j.exger.2022.112074
• Publication Date: 2022-12-22T16:34:45Z
• Authors: M.S. Valentine; C. Weigel; F. Kamga Gninzeko; C. Tho; M.H. Gräler; A.M. Reynolds; S. Spiegel; R.L. Heise
• Keywords: Proinflammatory cytokine

Ventilator-induced Lung Injury (VILI) is characterized by hypoxia, inflammatory cytokine influx, loss of alveolar barrier integrity, and decreased lung compliance. Aging influences structure function a predictive factor in the severity VILI; however, mechanisms aging that influence progression or increased susceptibility remain unknown. impacts immune system may increase inflammation healthy individuals. Recent studies suggest bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) enzyme degrades it S1P lyase (SPL) be involved pathologies including acute injury. It unknown whether SPL expression have been implicated inflammation, injury, cell apoptosis. We hypothesized injurious mechanical ventilation synergistically impair levels enhance amplifies damage diminishes pulmonary function. Young (2–3 mo) old (20–25 C57BL/6 mice were mechanically ventilated for 2 h using pressure-controlled (PCMV) at 45 cmH2O 35 cmH2O, respectively. assessed impact PCMV on several indications recruitment, activity. Furthermore, we evaluated protective effects inhibiting tetrahydroxybutylimidazol (THI) administration negative outcomes associated with exacerbated injury neutrophil influx was further due to aging. young nonventilated group. THI treatment reduced indicators resulted elevated tissue plasma from injured ventilation. CD80 CD206 activation markers interstitial macrophages also influenced THI. inhibition viable therapeutic approach patients requiring preventing regulating exaggerated response reducing