Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Clin Exp Allergy. 2011 Dec;41(12):1747-56. doi: 10.1111/j.1365-2222.2011.03852.x. Epub 2011 Sep 20.
Glucocorticosteroids (GCS) are used to treat bronchial asthma, but are not uniformly effective, especially in severe asthma. IL-13 is a T helper type 2 cytokine implicated in the pathogenesis of asthma, and IL-13 induces mucus production and goblet cell hyperplasia in airway epithelial cells. The effect of GCS on IL-13-induced mucin production is not well characterized.
The aim of this study was to evaluate the effect of dexamethasone (Dex), a potent synthetic GCS, on IL-13-induced MUC5AC mucin expression and goblet cell proliferation in differentiated normal human bronchial epithelial cells (NHBECs).
NHBECs were cultured for 14 days at an air-liquid interface with IL-13, with or without Dex. MUC5AC protein secretion and mRNA expression was determined using ELISA and quantitative real-time PCR. IL-8 production was assayed using ELISA. Histochemical analysis was performed using H&E and periodic acid-Schiff stain, and MUC5AC immunostaining.
Although Dex dose dependently inhibited IL-8 release induced by 5 ng/mL IL-13, Dex 0.001-1 μg/mL had no effect on IL-13 induced MUC5AC protein secretion or mRNA expression. Dex paradoxically increased MUC5AC induced by IL-13 at 0.5 and 1 ng/mL, but had no effect alone or with IL-13 at 0.1 ng/mL. Dex 0.001-1 μg/mL did not inhibit the differentiation of cells into goblet cells and MUC5AC-positive cells induced by IL-13.
Dex at therapeutic concentrations did not inhibit the effects of IL-13 on goblet cell differentiation, characteristic of severe asthma. Paradoxically, MUC5AC production was increased with lower dose IL-13 exposure. This may lead to airway mucus obstruction commonly seen in life-threatening asthma.
糖皮质激素（GCS）用于治疗支气管哮喘，但并非普遍有效，尤其是在严重哮喘中。IL-13 是一种 T 辅助型 2 细胞因子，与哮喘的发病机制有关，IL-13 可诱导气道上皮细胞中的黏液产生和杯状细胞增生。GCS 对 IL-13 诱导的粘蛋白产生的影响尚未得到很好的描述。
本研究旨在评估地塞米松（Dex），一种有效的合成 GCS，对分化的正常人支气管上皮细胞（NHBEC）中 IL-13 诱导的 MUC5AC 粘蛋白表达和杯状细胞增殖的影响。
在有或没有 Dex 的情况下，将 NHBEC 在气液界面培养 14 天，用 IL-13 处理。通过 ELISA 和实时定量 PCR 测定 MUC5AC 蛋白分泌和 mRNA 表达。通过 ELISA 测定 IL-8 产生。用 H&E 和过碘酸-Schiff 染色及 MUC5AC 免疫染色进行组织化学分析。
尽管 Dex 剂量依赖性地抑制了 5ng/ml IL-13 诱导的 IL-8 释放，但 0.001-1μg/ml Dex 对 IL-13 诱导的 MUC5AC 蛋白分泌或 mRNA 表达没有影响。Dex 反而增加了 0.5 和 1ng/ml IL-13 诱导的 MUC5AC，但单独或与 0.1ng/ml IL-13 一起无作用。0.001-1μg/ml Dex 不抑制 IL-13 诱导的细胞向杯状细胞分化和 MUC5AC 阳性细胞。
在治疗浓度下，Dex 不能抑制 IL-13 对杯状细胞分化的作用，这是严重哮喘的特征。相反，在较低剂量的 IL-13 暴露下，MUC5AC 的产生增加。这可能导致危及生命的哮喘中常见的气道黏液阻塞。
