Journal
PULMONARY PHARMACOLOGY & THERAPEUTICS
Volume 54, Issue -, Pages 77-86Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pupt.2018.12.004
Keywords
Hydrogen sulfide; Heme oxygenase-1; Acute lung injury; Lipopolysaccharide
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Funding
- National Natural Science Foundation of China [81570010, 81772045]
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GYY4137, a slow-releasing hydrogen sulfide (H2S) donor, has been reported to exert anti-inflammatory activity and protect against sepsis. Herne oxygenase-1 (HO-1) is an important anti-inflammatory heat shock protein and plays a similar effect on sepsis. This study investigated the role of GYY4137 in acute lung injury (ALI) via HO-1 regulation. Lung injury was assessed in mice challenged with intratracheal lipopolysaccharide (LPS) and the mechanism of anti-inflammatory effects of GYY4137 was investigated in mice and RAW264.7 cells, GYY4137 reduced the LPS-mediated pulmonary injury and neutrophil infiltration, and inhibited the LPS-induced production of proinflammatory cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Moreover, GYY4137 suppressed the LPS-evoked NF-kappa B activation in RAW264.7 cells. GYY4137, not time-expired GYY4137 significantly induced HO-1 expression compared with the LPS group. The beneficial effects of GYY4137 above were reversed by the HO-1 inhibitor tin protoporphyrin (SnPP). These results suggest an anti-inflammatory effect and a therapeutic role of GYY4137 in LPS-induced ALI via HO-1 regulation.
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