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Immunopharmacol Immunotoxicol. 2019 Apr;41(2):299-311. doi: 10.1080/08923973.2019.1593447. Epub 2019 Mar 25.

Effects of sitagliptin and vitamin D3 on T helper cell transcription factors and cytokine production in clinical subgroups of type 2 diabetes mellitus: highlights upregulation of FOXP3 and IL-37.

Author information

1
a Department of Immunology, School of Medicine , Hamadan University of Medical Sciences , Hamadan , Iran.
2
b Department of Internal Medicine, School of Medicine , Hamadan University of Medical Sciences , Hamadan , Iran.
3
c Molecular Immunology Research Group, Research Center for Molecular Medicine , Hamadan University of Medical Sciences , Hamadan , Iran.
4
d Neurophysiology Research Center , Hamadan University of Medical Sciences , Hamadan , Iran.

Abstract

Objective: Gene expression level of T helper cell transcription factors and cytokines production in type-2 diabetes mellitus (T2DM) patients treated with mono- or combined sitagliptin and vitamin D3 (VitD3) were evaluated. Methods: Fifty-four nephropathic and 57 non-nephropathic T2DM patients were divided into the subgroups based on their treatment with/without sitagliptin and VitD3. The expression of T-bet, RORγt, BCL6, and FOXP3 was evaluated using real-time PCR. The levels of IFN-γ, IL-6, IL-17, IL-21, TGF-β, and IL-37 were assessed in PBMC supernatants using ELISA. Results: The production of IFN-γ and IL-17 was increased in untreated (without sitagliptin and VitD3) nephropathic and non-nephropathic T2DM patients compared with healthy controls, whereas FOXP3 expression was decreased. Treatment with sitagliptin alone or in combination with VitD3 reduced the production of IFN-γ in the patients. Production of IL-17 and IL-21 and the expression of RORγt and BCL6 was diminished in patients treated with combined sitagliptin and VitD3, whereas the production of IL-37 and FOXP3 expression were increased in the patients treated with sitagliptin or sitagliptin plus VitD3. Conclusion: These data demonstrate that sitagliptin in combination with VitD3 may accelerate the process of T2DM treatment by exerting synergic anti-inflammatory effects on immune system through upregulation of FOXP3 and IL-37, and downregulation of RORγt and BCL6 as well as IFN-γ, IL-17 and IL-21 production. Combined sitagliptin and VitD3 can be safely utilized to modulate the inflammatory conditions of T2DM.

KEYWORDS:

T helper cell; T2DM; cytokine; sitagliptin; vitamin D3

PMID:
30907193
DOI:
10.1080/08923973.2019.1593447
[Indexed for MEDLINE]

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