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

Abstract

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. 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). 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. Histamine activated the IκBα/NF-κB pathway by promoting IκBα phosphorylation and inducing NF-κBp65 nuclear translocation, contributing to MUC5B overproduction and secretion.