The role of claudin 5 in a murine model of asthma
Background: The tight junction (TJ) protein, claudin 5 (CLDN5) is critical to the control of endothelial cellular polarity and pericellular permeability.In the past, the role of CLDN5 in asthma has had limited attention.
Objective: The aim of study was to identify the expression of CLDN 5 and response to steroid treatment in a mouse model of asthma (i.e. ovalbumin (OVA)-induced allergic lung inflammation) and in human lung microvascular endothelial cells (HLMVEC) and normal human bronchial epithelial (NHBE) cells.
Methods: Mice were treated with saline (sham), OVA sensitized and challenged (OVA), or OVA with dexamethasone. Lung CLDN5 levels were assessed with qRT-PCR, ELISA, immunoblotting, immunohistochemical stain, and confocal imaging. HLMVEC were treated with host dust mite peptidase (Der p1) or interleukin 4 (IL-4) and CLDN5 mRNA and transmembrane endothelial electrical resistance (TEER) measured.
Results: Airway inflammation, hyperresponsiveness, cytokines, and CLDN5 transcript and protein increased in OVA sensitized/challenged mice and these responses were reduced by dexamethasone treatment. The AKT1/FOXO1/CTNNB1 pathway was involved in CLDN5 protein expression. Der p1 increased CLDN5 protein expression in HLMVEC (but not NHBE) cells and decreased trans-endothelial electrical resistance. IL-4 also increased CLDN5 in HLMVEC, decreased TEER, and these effect were inhibited by dexamethasone.
Conclusion: CLDN5 is implicated in the pathogenesis of bronchial asthma and represent a potential target for therapeutic intervention.
Keywords: Tight junction, claudin 5, bronchial asthma