In:
Critical Care Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 8 ( 2017-08), p. e849-e857
Abstract:
Hydrogen sulfide reduces ventilator-induced lung injury in mice. Here, we have examined the underlying mechanisms of hydrogen sulfide-mediated lung protection and determined the involvement of cyclooxygenase 2, 15-deoxy Δ 12,14 -prostaglandin J2, and peroxisome proliferator-activated receptor gamma in this response. Design: Randomized, experimental study. Setting: University medical center research laboratory. Subjects: C57BL/6 mice and in vitro cell catheters. Interventions: The effects of hydrogen sulfide were analyzed in a mouse ventilator-induced lung injury model in vivo as well as in a cell stretch model in vitro in the absence or presence of hydrogen sulfide. The physiologic relevance of our findings was confirmed using pharmacologic inhibitors of cyclooxygenase 2 and peroxisome proliferator-activated receptor gamma. Measurements and Main Results: Mechanical ventilation caused significant lung inflammation and injury that was prevented in the presence of hydrogen sulfide. Hydrogen sulfide-mediated protection was associated with induction of cyclooxygenase 2 and increases of its product 15-deoxy Δ 12,14 -prostaglandin J2 as well as cyclooxygenase 2/15-deoxy Δ 12,14 -prostaglandin J2-dependent activation of peroxisome proliferator-activated receptor gamma. Hydrogen sulfide-dependent effects were mainly observed in macrophages. Applied mechanical stretch to RAW 264.7 macrophages resulted in increased expression of interleukin receptor 1 messenger RNA and release of macrophage inflammatory protein-2. In contrast, incubation of stretched macrophages with sodium hydrosulfide prevented the inflammatory response dependent on peroxisome proliferator-activated receptor gamma activity. Finally, application of a specific peroxisome proliferator-activated receptor gamma inhibitor abolished hydrogen sulfide-mediated protection in ventilated animals. Conclusions: One hydrogen sulfide-triggered mechanism in the protection against ventilator-induced lung injury involves cyclooxygenase 2/15-deoxy Δ 12,14 -prostaglandin J2-dependent activation of peroxisome proliferator-activated receptor gamma and macrophage activity.
Type of Medium:
Online Resource
ISSN:
0090-3493
DOI:
10.1097/CCM.0000000000002440
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
2034247-0
Permalink
