Vitamin A maintains the airway epithelium in a murine model of asthma by suppressing glucocorticoid-induced leucine zipper.

ABSTRACT

BACKGROUND: The effects of glucocorticoids (GCs) on the repair of the airway epithelium in asthma are controversial, and we previously reported that the GC dexamethasone (Dex) inhibits the repair of human airway epithelial cells and that this process is mediated by glucocorticoid-induced leucine zipper (GILZ) through MAPK-ERK signaling in vitro. Vitamin A (VA) is involved in the regulation of the MAPK-ERK pathway but has not been widely supplied during asthma treatment. It is unclear whether VA attenuates the negative regulation of GILZ on the MAPK-ERK pathway and maintains airway epithelium integrity during asthma treatment. METHODS: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) and subsequently treated with Dex, VA or intranasal inhalation of adenovirus sh-GILZ vectors. Indexes of airway epithelium integrity, including pathological alterations, pulmonary EGFR expression and airway hyperresponsiveness (AHR), were then measured. The expression of GILZ and key components of activated MAPK-ERK signals (p-Raf-1, p-MEK, and p-Erk1/2) were also detected. RESULTS: Dex failed to relieve OVA-induced asthma airway epithelium injury, as assessed through H&E staining, EGFR expression and AHR. Moreover, in the OVA-challenged mice treated with Dex, GLIZ expression was increased, whereas the ratios of p-Raf-1/Raf-1, p-MEK/MEK and p-Erk1/2/Erk1/2 were significantly decreased. Further study indicated that GILZ expression was decreased and that the ratios of p-Raf-1/Raf-1, p-MEK/MEK and p-Erk1/2/Erk1/2 were up-regulated in the GILZ-silenced OVA-challenged mice and VA-fed OVA-challenged mice, independent of Dex treatment. The airway epithelium integrity of the OVA-challenged mice was maintained by treatment with both VA and Dex. CONCLUSIONS: Vitamin A maintained the Dex-treated asthma airway epithelium via the down-regulation of GILZ expression and the activation MAPK-ERK signaling, and these effects might contribute to improving the effects of GC therapeutics on asthma.