Shiobara Taichi, Chibana Kazuyuki, Watanabe Taiji, Arai Ryo, Horigane Yukiko, Nakamura Yusuke, Hayashi Yumeko, Shimizu Yasuo, Takemasa Akihiro, Ishii Yoshiki
Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan.
Respir Res. 2016 Mar 14;17:28. doi: 10.1186/s12931-016-0342-7.
Type 2 helper T-cell cytokines including IL-13 play a central role in the pathogenesis of bronchial asthma (BA). During the course of our research, our attention was drawn to dipeptidyl peptidase-4 (DPP4) as one of the molecules that were induced from bronchial epithelial cells (BECs) by IL-13 stimulation. DPP4 could become a new biomarker or therapeutic target. The aim of this study was to investigate the expression of DPP4 in the asthmatic airway, and its role in the pathophysiology of asthma.
BECs were isolated from patients with inhaled corticosteroid-treated asthma (stBA) and inhaled corticosteroid-naïve asthma (snBA) using bronchoscopy. DPP4 mRNA expression in freshly isolated BECs and primary cultured BECs with or without IL-13 stimulation was investigated by microarray analysis and quantitative real-time PCR (qPCR). The distribution of DPP4 protein was determined by immunostaining of transbronchial lung biopsy specimens from asthma patients. The effect of recombinant human (rh) DPP4 on the proliferation of lung fibroblasts (HFL-1) and bronchial smooth muscle cells (BSMCs) was examined, as well as its effect on the production of fibronectin (FN).
DPP4 mRNA was strongly expressed in freshly isolated BECs in snBA, and its expression was significantly enhanced by IL-13 stimulation. DPP4 mRNA expression in BECs of snBA significantly correlated with exhaled nitric oxide. Biopsied tissues of the asthmatic airway revealed strong expression of DPP4 protein in BECs from snBA subjects. rhDPP4 stimulated the proliferation of HFL-1 and BSMCs, and it also enhanced production of FN from these airway cells.
DPP4 may be involved in the pathologic features of asthmatic airway inflammation and cell proliferation and FN production.
包括白细胞介素-13（IL-13）在内的2型辅助性T细胞细胞因子在支气管哮喘（BA）的发病机制中起核心作用。在我们的研究过程中，我们注意到二肽基肽酶-4（DPP4）是白细胞介素-13刺激支气管上皮细胞（BECs）诱导产生的分子之一。DPP4可能成为一种新的生物标志物或治疗靶点。本研究的目的是探讨DPP4在哮喘气道中的表达及其在哮喘病理生理学中的作用。
通过支气管镜从吸入糖皮质激素治疗的哮喘患者（stBA）和未使用吸入糖皮质激素的哮喘患者（snBA）中分离BECs。通过微阵列分析和定量实时聚合酶链反应（qPCR）研究新鲜分离的BECs以及有无IL-13刺激的原代培养BECs中DPP4 mRNA的表达。通过对哮喘患者经支气管肺活检标本进行免疫染色来确定DPP4蛋白的分布。检测重组人（rh）DPP4对肺成纤维细胞（HFL-1）和支气管平滑肌细胞（BSMCs）增殖的影响，以及其对纤连蛋白（FN）产生的影响。
DPP4 mRNA在snBA患者新鲜分离的BECs中强烈表达，并且其表达在IL-13刺激下显著增强。snBA患者BECs中DPP4 mRNA的表达与呼出一氧化氮显著相关。哮喘气道的活检组织显示snBA患者BECs中DPP4蛋白强烈表达。rhDPP4刺激HFL-1和BSMCs的增殖，并且还增强了这些气道细胞中FN的产生。
DPP4可能参与哮喘气道炎症、细胞增殖和FN产生的病理特征。
