Background: Airway epithelial cells are constantly exposed to intracellular and extracellular proteases that play a pivotal role in several airway diseases. Dermatophagoides pteronyssinus (Der p) 1 derived from house dust mite has protease activity that causes epithelial barrier defect and inflammatory response. Protease inhibitors released against proteases are involved in the maintenance of homeostasis. A disruption of the balance between proteases and protease inhibitors can lead to distortion of the cellular structures and cellular activities and thus culminate in disease processes. Although the effects of Der p 1 allergen on epithelial barrier integrity and inflammatory response are well-established, its contribution to protease inhibitor production is highly limited. Objective: This study aimed to determine the profile of the protease inhibitor response to Der p 1 allergen in human airway epithelial cells, A549 and BEAS-2B. Methods: Differentiated cells by the air-liquid interface were exposed to Der p 1 with or without Th2 type cytokines (IL-4 and IL-13). Gene expression of protease inhibitors was determined by qPCR at 2 different time points. Results: We found that the effect of allergen exposure on the protease inhibitor profile can vary depending on the antigen concentration, treatment duration, and the presence or absence of type 2 cytokines. Gene expressions of serine protease inhibitor (SERPIN)B3 and SERPINB4 were increased following Th2 cytokine stimulation in both cell types at both time points, whereas SERPINB2 and TFPI-2 expressions were induced by 24-h Der p 1 stimulation in both cells. Conclusions: Our study suggests that Der p 1 exposure of the airway epithelium may have consequences related to its protease activity in the presence as well as in the absence of Th2 cytokines in the microenvironment.
Int Arch Allergy Immunol

中文翻译：

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过敏原 (Der p 1) 刺激后气道上皮细胞中蛋白酶抑制剂的表达谱

背景：气道上皮细胞不断暴露于细胞内和细胞外蛋白酶，这些蛋白酶在几种气道疾病中起关键作用。来自屋尘螨的Dermatophagoides pteronyssinus (Der p) 1 具有蛋白酶活性，可导致上皮屏障缺陷和炎症反应。针对蛋白酶释放的蛋白酶抑制剂参与维持体内平衡。蛋白酶和蛋白酶抑制剂之间平衡的破坏会导致细胞结构和细胞活动的扭曲，从而导致疾病进程。尽管 Der p 1 过敏原对上皮屏障完整性和炎症反应的影响已得到充分证实，但其对蛋白酶抑制剂产生的贡献非常有限。客观的：本研究旨在确定蛋白酶抑制剂对人气道上皮细胞 A549 和 BEAS-2B 中 Der p 1 过敏原的反应概况。方法：通过气液界面分化的细胞暴露于有或没有 Th2 型细胞因子（IL-4 和 IL-13）的 Der p 1。通过 qPCR 在 2 个不同时间点确定蛋白酶抑制剂的基因表达。结果：我们发现过敏原暴露对蛋白酶抑制剂谱的影响可能因抗原浓度、治疗持续时间以及 2 型细胞因子的存在与否而异。丝氨酸蛋白酶抑制剂 ( SERPIN ) B3和SERPINB4的基因表达在两个时间点在两种细胞类型中的 Th2 细胞因子刺激后均增加，而SERPINB2和TFPI-2表达由两种细胞中的 24 小时 Der p 1 刺激诱导。结论：我们的研究表明，在微环境中存在和不存在 Th2 细胞因子的情况下，气道上皮细胞的 Der p 1 暴露可能会产生与其蛋白酶活性相关的后果。
Int Arch 过敏免疫