Original Article
Lipoxin A4 ameliorates alveolar fluid clearance disturbance in lipopolysaccharide-induced lung injury via aquaporin 5 and MAPK signaling pathway
Abstract
Background: A characteristic of acute lung injury (ALI) is the inflammatory damage of alveolar fluid transport. Lipoxins are endogenous lipids involving in the resolution of inflammation. It is found that lipoxin A4 (LXA4) has the distinct properties to improve the anti-edema and pro-resolution function in inflammation. Since aquaporins (AQPs) have essential roles in the integrity of barrier function during fluid transport, especially AQP5 in the maintaining of the epithelium permeability, the current study is aimed to evaluate the potential role of LXA4 in regulating alveolar fluid clearance (AFC) during fluid transport and the corresponding change of AQP5 in the lung.
Methods: ALI was induced by the lipopolysaccharide (LPS) intraperitoneal injection, and LXA4 treatment was given 8 hours after LPS administration. We investigated changes in the capacity of AFC, pro-inflammatory cytokine concentrations in bronchoalveolar lavage fluid (BALF) and the severity of ALI. Then AQP5 expression in lung tissue and potential regulatory pathways in LPS-induced ALI was explored.
Results: LXA4 treatment was found to inhibit AFC capacity, inflammatory cytokine release, partially, alleviate ALI severity, and restored AQP5 expression partially. Additionally, we found that LXA4 played a protective role by the inhibition of the phosphorylation of p38 and JNK.
Conclusions: In summary, our results suggest that LXA4 plays a protective role in lipopolysaccharide-induced ALI by restoring AFC capacity and upregulating AQP5 expression and inhibiting the phosphorylation of p38 and JNK. These findings suggest potential new mechanism of LXA4 as anti-inflammation therapy for the impairment of alveolar fluid transport in ALI.
Methods: ALI was induced by the lipopolysaccharide (LPS) intraperitoneal injection, and LXA4 treatment was given 8 hours after LPS administration. We investigated changes in the capacity of AFC, pro-inflammatory cytokine concentrations in bronchoalveolar lavage fluid (BALF) and the severity of ALI. Then AQP5 expression in lung tissue and potential regulatory pathways in LPS-induced ALI was explored.
Results: LXA4 treatment was found to inhibit AFC capacity, inflammatory cytokine release, partially, alleviate ALI severity, and restored AQP5 expression partially. Additionally, we found that LXA4 played a protective role by the inhibition of the phosphorylation of p38 and JNK.
Conclusions: In summary, our results suggest that LXA4 plays a protective role in lipopolysaccharide-induced ALI by restoring AFC capacity and upregulating AQP5 expression and inhibiting the phosphorylation of p38 and JNK. These findings suggest potential new mechanism of LXA4 as anti-inflammation therapy for the impairment of alveolar fluid transport in ALI.
