Decreased shedding dipeptidyl peptidase 4 from membrane in Hashimoto's thyroiditis

Int Immunopharmacol. 2020 Apr:81:106315. doi: 10.1016/j.intimp.2020.106315. Epub 2020 Feb 18.

Abstract

Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Autoimmune thyroid disease; Dipeptidyl peptidase 4; Hashimoto's thyroiditis; Kallikrein-related peptidase 5.

MeSH terms

  • Adult
  • Dipeptidyl Peptidase 4 / metabolism*
  • Enzyme Activation
  • Female
  • Gene Expression Regulation
  • Hashimoto Disease / metabolism*
  • Hashimoto Disease / pathology
  • Humans
  • Interferon-gamma / metabolism
  • Kallikreins / metabolism*
  • Leukocytes, Mononuclear / physiology*
  • Male
  • Middle Aged
  • Proteolysis
  • Young Adult

Substances

  • Interferon-gamma
  • Dipeptidyl Peptidase 4
  • KLK5 protein, human
  • Kallikreins