NLRP3 inflammasome-mediated modulation of E-cadherin and β-catenin in airway epithelial dysfunction in a lipopolysaccharide-induced murine acute lung-injury model

E-cadherin and β-catenin are key components of adherens junctions (AJ), which serve to ensure epithelial integrity. Disrupted expression of these proteins contributes to the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome. In this study, we aimed to examine whether the NLRP3 inflammasome mediates AJ dysfunction in a lipopolysaccharide (LPS)-induced murine ALI model. Male BALB/c mice were intratracheally administered LPS. MCC950, a specific inhibitor of NLRP3, was injected intraperitoneally after the LPS challenge. Lungs were collected for histology, immunohistochemistry, and western blotting to assess NLRP3, E-cadherin, and β-catenin expression. Bronchoalveolar lavage fluid (BALF) was collected and soluble E-cadherin (sE-cadherin) was detected. LPS markedly upregulated pulmonary NLRP3, ASC, and caspase-1 expression, and this was accompanied by reduced expressions of E-cadherin and β-catenin and increased production of sE-cadherin. MCC950 inhibition of the NLRP3 inflammasome attenuated LPS instillation-induced alveolar-capillary permeability, oedema and neutrophilic inflammation, as well as decreased levels of total protein concentration, interleukin (IL)-6, IL-1β, and tumour necrosis factor-α in BALF. Furthermore, it restored epithelial E-cadherin and β-catenin expressions and inhibited the release of sE-cadherin. The NLRP3 inflammasome mediated airway epithelial E-cadherin and β-catenin dysfunction in an LPS instillation-induced murine ALI model.