Egr-1 regulates muc5ac expression through activator protein-1 (AP-1) in chronic airway inflammation diseases

Background: Muc5ac, a major constituent of mucus, was reported to be regulated by DNA binding protein AP-1 in its promoter area. Evidence has also shown that early growth response factor 1 (Egr-1) could regulate AP-1 expression and activity. Aims and Objectives: The aim of this study was to investigate mechanisms of Egr-1, AP-1 and muc5ac in airway inflammation diseases. Methods: Egr1, AP-1, muc5ac levels were measured by Western blot and Q-PCR under treatment with cigarette smoke extract (CSE)/interleukin-13 (IL-13) in vitro. The regulatory mechanisms were investigated using Co-IP, ChIP and confocal microscopy. The in vivo animal experiments in Egr-1/AP-1 axis were observed by western blot and mucus staining of asthma model and CSE model in WT and Egr1-/- mice. Results: Egr1-AP-1 interactions definitely regulated muc5ac production in lung epithelial cell lines with CSE and IL-13 treatment. Egr-1 siRNA transfection resulted in significant down-regulation of muc5ac. Co-IP and ChIP showed that Egr-1 could bind to AP-1 and indirectly interact on muc5ac promoter. In asthma and CSE model, we observed higher levels of Egr-1, AP-1, and mucus production in lung tissue, whereas low levels in Egr1 -/- mice. Conclusions: Our research indicated that mucus might be initiated by Egr-1 and regulated by Egr-1/AP-1 axis in airway epithelial cellsand this might be a pathogenic mechanism of mucus hyper-secretion in chronic airway inflammation diseases.