Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, China.
Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, China.
Int Immunopharmacol. 2020 Apr;81:106315. doi: 10.1016/j.intimp.2020.106315. Epub 2020 Feb 18.
This study aimed to determine the concentration and enzymatic activity of dipeptidyl peptidase 4 (DPP4) in serum and peripheral blood mononuclear cells (PBMCs) from patients with Hashimoto's thyroiditis (HT) and to explore the potential mechanism of the abnormal DPP4 in HT development.
A total of 33 newly diagnosed HT patients and 31 age- and sex-matched healthy controls were enrolled. Clinical characteristics and thyroid function data were collected for all participants. Serum DPP4 and kallikrein-related peptidase 5 (KLK5) concentrations were measured by sandwich enzyme-linked immunosorbent assay. DPP4 enzymatic activities in serum and PBMCs were determined by enzymatic assay. DPP4, KLK5 and interferon (IFN)-γ mRNA expression levels in PBMCs were evaluated by quantitative real-time polymerase chain reaction.
Serum DPP4 level and activity were significantly lower in the HT group compared with the control group. However, DPP4 mRNA expression was significantly increased and both serum KLK5 concentration and KLK5 mRNA expression in PBMCs were significantly decreased in HT patients. Correlation analyses revealed that DPP4 concentration was positively correlated with DPP4 enzymatic activity in serum. No significant difference in DPP4 activity was found in PBMCs. DPP4 enzymatic activity in PBMCs was negatively correlated with DPP4 enzymatic activity in serum. IFN-γ mRNA expression in PBMCs was significantly increased in HT patients.
DPP4 is involved in the development and pathological process of HT. Decreased cleavage of membrane-anchored DPP4 by KLK5 may be responsible for the decreased serum DPP4 levels in HT patients.
本研究旨在测定桥本甲状腺炎(HT)患者血清和外周血单个核细胞(PBMC)中二肽基肽酶 4(DPP4)的浓度和酶活性,并探讨 DPP4 在 HT 发病机制中的潜在作用。
共纳入 33 例新诊断的 HT 患者和 31 名年龄和性别匹配的健康对照者。所有参与者均采集临床特征和甲状腺功能数据。采用夹心酶联免疫吸附试验测定血清 DPP4 和激肽释放酶相关肽 5(KLK5)浓度。通过酶联免疫吸附试验测定血清和 PBMC 中的 DPP4 酶活性。采用实时定量聚合酶链反应评估 PBMC 中 DPP4、KLK5 和干扰素(IFN)-γ mRNA 的表达水平。
与对照组相比,HT 组血清 DPP4 水平和活性显著降低。然而,HT 患者的 DPP4 mRNA 表达显著增加,血清 KLK5 浓度和 PBMC 中 KLK5 mRNA 表达均显著降低。相关性分析表明,血清中 DPP4 浓度与 DPP4 酶活性呈正相关。PBMC 中 DPP4 活性无显著差异。PBMC 中 DPP4 酶活性与血清中 DPP4 酶活性呈负相关。HT 患者 PBMC 中 IFN-γ mRNA 表达显著增加。
DPP4 参与 HT 的发生和病理过程。KLK5 对膜锚定的 DPP4 的水解减少可能导致 HT 患者血清 DPP4 水平降低。