Modulation of epithelial sodium channel in human alveolar epithelial cells by lipoxin A4 through AhR-cAMP-dependent pathway

Purpose: To investigate the effect of lipoxin A4 (LXA4) on the expressions of protein and mRNA of alveolar epithelial sodium channel (ENaC) in normal and lipopolysaccharide (LPS)-stimulated A549 cells.Methods: A549 cell-lines were randomized into 11 groups (N = 8) and treated. EnaC level was evaluated by Western blot. Total RNA was extracted and reverse-transcribed and then levels of ENaC mRNA, cGMP and cAMP in the cells were determined.Results: LXA4 (10-7mol/L) increased the expressions of α-subunit of ENaC relative to LPS group. In addition, LXA4 significantly up-regulated the expression of mRNAs of α, β and γ subunits of ENaC (p < 0.01). The level of cAMP was increased in LXA4 group, but significantly reduced in LPS group relative to control group (p < 0.05). However, treatment with LXA4 annulled the increased cAMP concentration, compared with LPS group (p < 0.05)Conclusion: These results show that LXA4 influences ENaC up-regulation in normal and LPS stimulated A549 alveolar epithelial cells.Keywords: Acute lung injury, Alveolar epithelial sodium channel, Lipoxin A4, AhR, cAMP, cGM