Karaaslan Cagatay, Karaguzel Dilara, Sarac Basak Ezgi, Sucularli Ceren, Bilgic Hayriye Akel, Kalayci Omer
Department of Biology, Molecular Biology Section, Faculty of Science, Hacettepe University, Ankara, Turkey.
Department of Bioinformatics, Institute of Health Sciences, Hacettepe University, Ankara, Turkey.
Int Arch Allergy Immunol. 2022;183(1):25-33. doi: 10.1159/000518170. Epub 2021 Aug 20.
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.
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.
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.
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.
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.
气道上皮细胞不断暴露于细胞内和细胞外蛋白酶中,这些蛋白酶在多种气道疾病中起关键作用。源自屋尘螨的粉尘螨(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体内稳态的维持。蛋白酶与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,从而最终引发疾病进程。尽管Der p 1变应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却非常有限。
本研究旨在确定人气道上皮细胞A549和BEAS-2B中蛋白酶抑制剂对Der p 1变应原反应的概况。
通过气液界面分化的细胞暴露于有或无Th2型细胞因子(IL-4和IL-13)的Der p 1中。在2个不同时间点通过qPCR测定蛋白酶抑制剂的基因表达。
我们发现,变应原暴露对蛋白酶抑制剂概况的影响可能因抗原浓度、处理持续时间以及2型细胞因子的存在与否而有所不同。在两个时间点的两种细胞类型中,Th2细胞因子刺激后丝氨酸蛋白酶抑制剂(SERPIN)B3和SERPINB4的基因表达均增加,而在两种细胞中,24小时Der p 1刺激诱导了SERPINB2和TFPI-2的表达。
我们的研究表明,在微环境中存在或不存在Th2细胞因子的情况下,气道上皮暴露于Der p 1可能会因其蛋白酶活性而产生相关后果。