1 research outputs found
Supplementary Material for: Inhibition of Rac1 Signaling Downregulates Inflammasome Activation and Attenuates Lung Injury in Neonatal Rats Exposed to Hyperoxia
<p><b><i>Background:</i></b> Inflammatory injury, particularly the
production of active interleukin (IL)-1β plays a major role in the
pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. The
release of active IL-1β is controlled by posttranscriptional
modifications of its proform (pro-IL-1β) through the inflammasome. Rac1
is a member of the Rho family of GTPases that regulate the inflammatory
process. <b><i>Objective:</i></b> This study tested the hypothesis that
Rac1 signaling increases inflammasome activation that results in
damaging inflammation, and that the inhibition of Rac1 signaling
prevents lung injury, by inhibiting inflammasome activation in a newborn
rat model of BPD induced by hyperoxia. <b><i>Methods:</i></b> Newborn rat pups were exposed to room air or hyperoxia (85% O<sub>2</sub>)
and received daily intraperitoneal injections of placebo (normal
saline) or NSC23766, a specific Rac1 inhibitor, for 10 days. The effects
on lung inflammation, alveolarization, vascular development, vascular
remodeling, right ventricular systolic pressure, and right ventricular
hypertrophy (RVH) were then assessed. <b><i>Results:</i></b> Hyperoxia
exposure upregulated Rac1 and increased the production of active IL-1β,
which was accompanied by increasing expression of the inflammasome. In
addition, hyperoxia induced the pathological hallmarks of BPD. However,
treatment with NSC23766 significantly decreased inflammasome activation
and macrophage infiltration, improved alveolar and vascular development,
and reduced pulmonary vascular remodeling and RVH. <b><i>Conclusion:</i></b>
These results indicate that Rac1 signaling regulates the expression of
the inflammasome and plays a pivotal role in the pathogenesis of
hyperoxia-induced neonatal lung injury. Therefore, targeting Rac1
signaling may provide a novel strategy to prevent and treat BPD in
preterm infants.</p