Abstract
Purpose: To investigate the effect of juglone on LPS induced lung injury in a mouse model and in TC 1cell line.Methods: Edema formation in lungs were measured by determination of lung wet/dry weight. Expressions of various proteins were assessed by western blot assay, while Sirt1 level was assessed using immunohistochemistry. Mice were randomly assigned to nine groups of 10 mice each: normal control, untreated and seven juglone treatment groups. Acute lung injury was induced in mice by injecting LPS (10 mg/kg) via intraperitoneal route (ip). The treatment groups were given 10, 20, 30, 40, 50, 60 and 100 μM of juglone, ip, respectively.Results: The levels of MMP-9, IL-6, IL-1β and iNOS were significantly higher in acute lung injury induced mice compared than the control group (p < 0.05). Treatment of the mice with juglone significantly decreased LPS-induced up-regulation of inflammatory cytokines in a dose-dependentmanner. The production of inflammatory cytokines was almost completely inhibited in the mice treated with 100 mg/kg dose of juglone, while treatment of the LPS-stimulated TC 1 cells with juglone upregulated the expression of Sirt1 mRNA. Down-regulation of Sirt1 expression by siRNA inhibited the effect of juglone on LPS-induced increase in inflammatory cytokine production.Conclusion: Juglone prevents lung injury in mice via up-regulation of Sirt1 expression. Therefore, juglone might be useful for the development of a treatment strategy for lung injury.
 Keywords: Inflammatory, Sirtuin, Edema, Cytokines, Lung injury, TC 1 lung alveolar epithelial cells, Sirt1
Highlights
Acute lung injury is generally a complicated stage of sepsis leading to the dysfunction of pulmonary tissues and has more than 50% mortality rate [1]
Targeting Sirtuin 1 (Sirt1) gene expression by silencerRNA promotes the secretion of cytokines and its activation suppresses the level of TNF- α, monocyte chemo-attractant protein-1 and IL-8 [9]
These results suggest that juglone inhibits edema since accumulation of water is the characteristic feature of lung edema
Summary
Acute lung injury is generally a complicated stage of sepsis leading to the dysfunction of pulmonary tissues and has more than 50% mortality rate [1]. In mice LPS administration has been found to initiate inflammatory reactions which were followed by the lung injury [6]. Acute lung injury was established in mice by injecting 10 mg/kg dose LPS through intraperitoneal route. After 1 h of LPS injection, the mice in treatment groups were given 10, 20, 30, 40, 50, 60 and 100 μM of juglone intraperitoneally. The present study investigated the role of juglone in inhibition of acute lung injury caused by LPS in the mice. Five mice from each group were sacrificed at 16 h of juglone injection by isoflurane anaesthesia. Five mice from each group were sacrificed following juglone treatment using isoflurane anaesthesia. The tissues were washed with PBS and incubated for 50 min with horseradish peroxidase-labeled secondary antibody for determination Sirt expression. SPSS version 13.0 (SPSS, Inc., Chicago, IL, USA) was used for the statistical analysis, and p < 0.05 were taken to indicate statistically significant differences
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