Mucin 5 Subtype AC Expression and Upregulation in the Nasal Mucosa of Allergic Rhinitis Rats

Abstract

Objective

To elucidate the functions of nuclear factor kappa B (NF-κB) in mucin hypersecretion in allergic rhinitis (AR), we examined the in vivo effects of an NF-κB inhibitor, ammonium pyrrolidine dithiocarbamate (PDTC), on mucin 5 subtype AC (MUC5AC) expression in the nasal mucosa of ovalbumin-sensitized rats.

Study Design

Randomized animal study.

Setting

Academic medical center.

Subjects and Methods

Sprague Dawley rats were randomized into a control group (group A), an AR model group (group B), and an AR model treated with an NF-κB inhibitor (group C). Rats in groups B and C were sensitized systemically and locally by ovalbumin injection and inhalation, whereas group A was treated with normal saline in place of ovalbumin. Pyrrolidine dithiocarbamate (100 mg/kg/d) was given to group C by intraperitoneal injection for 5 days. NF-κBp65, MUC5AC, tumor necrosis factor (TNF)–α, and interleukin (IL)–6 were detected by immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay, or real-time polymerase chain reaction.

Results

NF-κB was activated in group B, and significant NF-κBp65 protein was expressed in the nucleus of cells from the nasal mucosa, resulting in upregulated transcription from TNF-α and IL-6 genes, as well as increased contents of TNF-α and IL-6 in the nasal lavage fluids. Pyrrolidine dithiocarbamate inhibited nuclear localization of NF-κBp65 and subsequent downregulation of the transcription and secretion of TNF-α and IL-6. MUC5AC was upregulated in group B but reduced in a time-dependent manner after inhibition of NF-κB activation.

Conclusion

NF-κB activation might induce MUC5AC hypersecretion in AR rats by inflammatory cytokines TNF-α and IL-6.