Department of Anatomy, Medical College, China Three Gorges University, Yichang City, Hubei Province, China.
Otolaryngol Head Neck Surg. 2012 Dec;147(6):1012-9. doi: 10.1177/0194599812460977. Epub 2012 Sep 12.
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.
Randomized animal study.
Academic medical center.
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.
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.
NF-κB activation might induce MUC5AC hypersecretion in AR rats by inflammatory cytokines TNF-α and IL-6.
通过研究核因子-κB（NF-κB）抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）对卵清蛋白致敏大鼠鼻黏膜黏蛋白 5 亚型 AC（MUC5AC）表达的体内作用，阐明 NF-κB 在变应性鼻炎（AR）中黏液高分泌的作用机制。
随机动物研究。
学术医疗中心。
将 Sprague Dawley 大鼠随机分为对照组（A 组）、AR 模型组（B 组）和 AR 模型 NF-κB 抑制剂治疗组（C 组）。B 组和 C 组大鼠通过卵清蛋白全身和局部注射致敏，而 A 组用生理盐水替代卵清蛋白处理。C 组大鼠腹腔内注射 PDTC（100mg/kg/d）5 天。采用免疫组化、Western blot、酶联免疫吸附试验或实时聚合酶链反应检测 NF-κBp65、MUC5AC、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6。
B 组 NF-κB 被激活，鼻黏膜细胞的细胞核中出现明显的 NF-κBp65 蛋白，导致 TNF-α和 IL-6 基因转录上调，鼻灌洗液中 TNF-α和 IL-6 含量增加。PDTC 抑制 NF-κBp65 的核定位及随后 TNF-α和 IL-6 的转录和分泌下调。B 组 MUC5AC 表达上调，但 NF-κB 激活抑制后呈时间依赖性降低。
NF-κB 激活可能通过炎症细胞因子 TNF-α和 IL-6 诱导 AR 大鼠 MUC5AC 过度分泌。
