Search

Objective: The probably effects of sitagliptin and vitamin D3 (VitD3) on proliferation capacity and cytokines production were investigated in type 2 diabetes mellitus (T2DM) in vitro., Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with T2DM and 26 healthy controls (HCs). CFSE-labeled PBMCs stimulated with phytohamagglutinin (PHA, 5 μg/mL) in the presence/absence of sitagliptin (200 mg/mL) with/without VitD3 (10 -8  M) for 4 days. The proliferation of CD4 + T helper cells and non-CD4 + cells was analyzed using flow cytometry. The supernatant levels of IFN-γ, IL-17, IL-4, TGB-β and IL-37 were detected using ELISA., Results: The proliferation of CD4 + T cells in response to PHA was higher in T2DM patients compared with HCs. The production of IFN-γ and IL-17 in PHA-stimulated cultures was higher, and the levels of IL-4 and IL-37 were lower in T2DM patients compared to HCs. The addition of sitagliptin or VitD3 to the cultures decreased the CD4 + T cells and non-CD4 + cells proliferation in patients and HCs. Sitagliptin with VitD3 was more effective in suppression of proliferation, decreasing of IL-17 and enhancing of IL-37 production., Conclusion: Sitagliptin plus VitD3 effectively reduces the proliferative T cells response and modulates pro-inflammatory/anti-inflammatory cytokines production.

Studies indicated that imbalance of proinflammatory and anti-inflammatory cytokines may contribute to development of type 2 diabetes mellitus (T2DM). We hypothesized that sitagliptin and VitD3 may exert more anti-inflammatory effects on the regulation of cytokine balance in T2DM. Nonnephropathic and nephropathic T2DM patients were divided into the subgroups, based on treatments. The effect of 8 months sitagliptin, alone or together with 2 months of VitD3, on serum IFN-γ, IL-4, IL-17, IL-6, IL-21, TGF-β, and IL-37 levels was determined using enzyme-linked immunosorbent assay. Increased levels of interferon (IFN)-γ and IL-17 in untreated (without sitagliptin and VitD3) nephropathic and nonnephropathic patients and decreased levels of IL-37 in untreated nephropathic patients were observed compared with healthy controls. Treatment with sitagliptin plus VitD3 reduced the levels of IFN-γ and IL-17 in both nonnephropathic and nephropathic patients compared with untreated patients. The level of IL-37 was enhanced in patients treated with sitagliptin or sitagliptin plus VitD3, compared with untreated patients. Sitagliptin plus VitD3 treatment increased the levels of IL-4 in nonnephropathic patients. These findings indicated that the sitagliptin plus VitD3 was more effective to reduce the increased proinflammatory IFN-γ and IL-17 cytokines in T2DM patients.

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.

1 α, 25-dihydroxyvitamin D3 (VitD3) has been suggested to have strong modulatory properties in the immune system. Researchers in the present study primarily aimed to understand the effect of VitD3 on human CD4 + T cell proliferation in antigen presenting cells (APCs) free condition in vitro. The effect of VitD3 on intracellular cytokine responses trend to Th1, Th2, Th17 and Th22 was evaluated using the flow cytometry. Moreover the effect of VitD3 on the expression of inhibitory markers such as PD1, PD-L1, and CTLA4 which are induced upon polyclonal T cell receptor (TCR) activation on CD4 + T cells, was assessed. We observed that the stimulation of CD4 + T cells with VitD3, suppressed proliferation capacity, enhanced the expression of PD1, PD-L1 and CTLA4 inhibitory markers on CD4 + T cells, and diminished the percentage of pro-inflammatory cytokines including, IFN-γ, IL-17, and IL-22 except IL-4 in CD4 + T cells. The data suggested a potential insight into the consideration of VitD3 in the prevention/control of pro-inflammatory immune response/autoimmune disorders., (Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Regulatory T cells were investigated in early-onset (EO) and late-onset (LO) myasthenia gravis patients with anti-acetylcholine receptor antibody (AChR-MG). Alterations in PD-1 and PD-L1 on CD4 + CD25 ++ (Treg) and responder T cells (Tresp, CD4 + CD25 − ) were observed in LOMG patients. GITR was decreased on CD4 + CD25 ++ of all patients. Decrease of FOXP3 was associated with lower phosphorylation of STAT5.1,25-dihydroxyvitamin D3 (VitD3) increased suppression in co-culture with a stronger effect in patients by acting possibly both on cell groups. Changes in surface molecules and intracellular pathways contribute to the defects of Treg in non-thymomatous AChR-MG and VitD3 can have modulatory effects. [ABSTRACT FROM AUTHOR]