Abstract
Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.
Highlights
Sepsis is a systemic and deleterious inflammatory response elicited by microbial infection [1,2,3]
Results indicated that LPS (0.5 μg/mL) stimulation for 24 h of Mouse peritoneal macrophages (MPMs) robustly increased the secretion of both interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) into medium (Figures 1(d) and 1(e), resp.)
The osthole-induced inhibition of cytokine secretion was associated with inhibition of the transcription of IL-6 and TNF-α (Figures 1(f) and 1(g))
Summary
Sepsis is a systemic and deleterious inflammatory response elicited by microbial infection [1,2,3]. The number of reported cases of sepsis continues to increase by 5 ~ 10% each year [4], making it one of the leading causes of death in intensive care facilities [5] Among these case reports, approximately 30% of patients progress to multiorgan dysfunction syndrome (MODS) with 18% developing acute lung injury (ALI) [6,7,8]. ALI is a severe form of diffuse lung disease described as a clinical syndrome of acute respiratory failure with high morbidity and mortality [9] It is characterized with persistent pulmonary inflammation [10] and increase in microvascular permeability [11]. Our findings would provide important insight on potential new therapeutic approaches for inflammation-related lung injury
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