Effect of Brefeldin A in acute lung injury induced by lipopolysaccharide

Objective To explore the effect of Brefeldin A in acute lung injury induced by lipopolysaccharide. Methods Mice alveolar macrophages (MH-S) and epithelial cells (MLE-12) were treated with Brefeldin A of 1, 10, 100 μM respectively, and then treated with LPS 500 ng/ml. The cell supernatants of 3, 6, 9 and 24 h were collected and the content of tumor necrosis factor-α (TNF-α) in MH-S and the chemokine KC in MLE-12 were determined. ICR mice were randomly divided into normal saline control group (group Normal), model group (group LPS), dexamethasone group (group Dex, 5 mg/kg) and brefeldin A group (group BFA, 10 mg/kg). Each group had 12 mice. The ALI mouse model was induced by instilling intratracheally LPS 2 mg/kg. The physiological saline group was given equal volume of normal saline. After 6 h, lung tissue and alveolar lavage fluid (BALF) were harvested, lung pathology changes were observed, white blood cell and albumin content and tumor necrosis factor α (TNF-α),interleukin-1β (IL-1β), interleukin 6 (IL-6) in BALF were determined, myeloperoxidase (MPO) activity, cAMP content and the changes of phosphorylation levels of protein kinases of ERK, p38 and JNK in MAPK signaling pathway in lung homogenates were detected by ELISA. Results BFA significantly reduced the release of TNF-α in MH-S and the production of KC in MLE-12 cells (P<0.001). BFA could significantly improve the pathological changes of lung tissue and decrease the content of white blood cells(P<0.001) and TNF-α content (P<0.05). However, there were no significant effects on albumin, IL-1β and IL-6 in BALF, and the activity of MPO in lung tissue was significantly decreased (P<0.05), the level of cAMP was significantly increased (P<0.001). Brefeldin A could significantly inhibit the phosphorylation of ERK (P<0.05). Conclusion Brefeldin A may have a protective effect on acute lung injury, and its mechanism may be related to inhibiting the release of related inflammatory factors, increasing intracellular cAMP content and inhibiting the phosphorylation of ERK.