MUC5AC expression is significantly increased in allergic and inflammatory airway diseases. IL 36 gamma is predominantly expressed in airway epithelial cells and plays an essential role in innate and adaptive immune responses. IL-36 gamma is induced by many inflammatory mediators, including cytokines and bacterial and viral infections. However, the association between IL-36 gamma and mucin secretion in human airway epithelial cells has not yet been thoroughly investigated.

This study’s objective was to determine whether IL-36 gamma might play a role in regulating mucin secretion in airway epithelial cells. We investigated the effect and short signaling pathway of IL-36 gamma on MUC5AC expression in human airway epithelial cells.

Enzyme immunoassay, immunoblot analysis, immunofluorescence staining, reverse transcriptase-PCR, and real-time PCR were performed on mucin-producing human airway epithelial NCI-H292 cells and human nasal epithelial cells after pretreatment with IL-36 gamma, several specific inhibitors, or siRNA.

IL-36 gamma induced MUC5AC expression and activated the phosphorylation of ERK 1 and 2, p38, and NF–kappa B. IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF–kappa B significantly attenuated IL-36 gamma induced MUC5AC expression.

The study concluded that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF–kappa B pathway in human airway epithelial cells.

Reference: https://journals.sagepub.com/doi/full/10.1177/1945892418762844