The role for human nasal epithelial nuclear factor kappa B activation in histamine-induced mucin 5 subtype B overproduction

Abstract

Background: Mucin 5 subtype B (MUC5B) is 1 of the major mucins secreted by airway epithelial cells. We sought to determine the effect of histamine on MUC5B expression in human nasal epithelial cells. Methods: Human nasal epithelial cells from allergic rhinitis patients were cultured, and stimulated with 4 concentrations of histamine, or pretreated with a specific nuclear factor-kappa B (NF-κB) inhibitor (Bay11-7082) before histamine stimulation. Immunocytochemistry and Western blotting were used to detect phosphorylated inhibitor of kappa B alpha (p-IκBα), NF-κBp65 and MUC5B protein. MUC5B content in supernatants was assayed by enzyme-linked immunosorbent assay (ELISA). Results: Histamine promoted IκBα phosphorylation and NF-κBp65 nuclear translocation. A concentration-dependent histamine-induced increase of MUC5B protein was observed, and its content in supernatants was upregulated in a concentration-dependent fashion, but these effects were attenuated by Bay11-7082. Conclusion: Histamine activated the IκBα/NF-κB pathway by promoting IκBα phosphorylation and inducing NF-κBp65 nuclear translocation, contributing to MUC5B overproduction and secretion.