The Relationship between Type 1 Diabetes Mellitus, TNF-α, and IL-10 Gene Expression

Haber, Jesselina Francisco dos Santos; Barbalho, Sandra Maria; Sgarbi, José Augusto; Haber, Rafael Santos de Argollo; Lábio, Roger Willian de; Laurindo, Lucas Fornari; Chagas, Eduardo Federighi Baisi; Payão, Spencer Luíz Marques

doi:10.3390/biomedicines11041120

Cited by 14 publications

(7 citation statements)

References 64 publications

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“…Previous study has found that the expression of TNF‐ α is negatively correlated with bone integration, while the expression of IL‐10 plays a positive role in bone integration. [ 36 ] Moreover, IL‐1β, well‐known for its capacity to incite pro‐inflammatory immune responses, carries the potential to disrupt cellular function and viability, thereby impeding tissue healing processes. [ 37 ] Moreover, NLRP3 has been implicated in promoting the development of diabetes and its complications.…”

Section: Resultsmentioning

confidence: 99%

Endowing Polyetheretherketone with Anti‐Infection and Immunomodulatory Properties through Guanidination Carbon Dots Modification to Promote Osseointegration in Diabetes with MRSA Infection

Bai,

Zhang,

Xiao

et al. 2023

Adv Healthcare Materials

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Methicillin‐resistant Staphylococcus aureus (MRSA) infection and compromised immunity are the severe complications associated with implantation surgery in diabetes mellitus. Enhancing the antibacterial and immunomodulatory properties of implants represents an effective approach to improve the osseointegration of implant in diabetes mellitus. Herein, guanidination carbon dots (GCDs) with antibacterial and immunoregulatory functions are synthesized. The GCDs demonstrate killing effect on MRSA without detectable induced resistance. Additionally, they promote the polarization of macrophages from the M1 to M2 subtype, with the inhibiting pro‐inflammatory cytokines and promoting anti‐inflammatory factors. Correspondingly, GCDs are immobilized onto sulfonated polyether ether ketone (SP@GCDs) using a polyvinyl butyraldehyde (PVB) coating layer through soaking‐drying technique. SP@GCDs maintain stable antibacterial efficacy against MRSA for six consecutive days and retain the immunomodulatory function, while also possessing the long‐term storage stability and biocompatibility of more than 6 months. Moreover, SP@GCDs significantly promote the proliferation and mineralization of osteoblasts. SP@GCDs facilitate osteogenesis through immunoregulatory. Additionally, SP@GCDs exert stable antibacterial and immune regulatory functions in implantation site of a diabetes rat, effectively promoting implant osseointegration regardless of the MRSA infection. These findings provide valuable insights into implant modification through designing nanomaterials with multifunction for enhancing osseointegration of diabetes mellitus, suggesting the promising clinical application prospects.

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Section: Resultsmentioning

confidence: 99%

Endowing Polyetheretherketone with Anti‐Infection and Immunomodulatory Properties through Guanidination Carbon Dots Modification to Promote Osseointegration in Diabetes with MRSA Infection

Bai,

Zhang,

Xiao

et al. 2023

Adv Healthcare Materials

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“…The role of cytokines in the pathophysiology of T1D is complex and not fully understood. Recent studies suggest that cytokines play an important role in the pathogenesis of the disease [ 21 , 30 , 31 , 32 ]. Most of the studied inflammatory markers have been shown to change gradually over time [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…One study found that plasma TNF-α levels were significantly higher in diabetic patients than in healthy subjects. Additionally, TNF-α levels positively correlated with age [ 31 ]. Available data on the relationship between TNF-α and glycemic control in type 1 diabetes are somewhat conflicting.…”

Section: Introductionmentioning

confidence: 99%

“…Poor glycemic control in diabetes results in increased oxidative stress [ 31 , 38 ] and increased protein glycation. This has been linked to cytokine activity, including TNF-α, interleukin-6 (IL-6), and interleukin-12 (IL-12).…”

Section: Introductionmentioning

confidence: 99%

“…IL-10 gene expression was found to be significantly increased in patients with ketoacidosis and has been shown to have a positive correlation with HbA1c levels. In addition, studies have demonstrated a negative correlation between IL-10 expression and patient age at the time of diabetes diagnosis [ 31 ]. This cytokine is an important regulator of immunity during infection, playing a key role in reducing or terminating inflammation and resulting in host protection [ 50 , 51 ].…”

Section: Introductionmentioning

confidence: 99%

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The Impact of Metabolic Memory on Immune Profile in Young Patients with Uncomplicated Type 1 Diabetes

Neubauer-Geryk,

Wielicka,

Myśliwiec

et al. 2024

IJMS

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Metabolic memory refers to the long-term effects of achieving early glycemic control and the adverse implications of high blood glucose levels, including the development and progression of diabetes complications. Our study aimed to investigate whether the phenomenon of metabolic memory plays a role in the immune profile of young patients with uncomplicated type 1 diabetes (T1D). The study group included 67 patients with uncomplicated type 1 diabetes with a mean age of 15.1 ± 2.3 years and a minimum disease duration of 1.2 years. The control group consisted of 27 healthy children and adolescents with a mean age of 15.1 ± 2.3 years. Patients were divided into three groups according to their HbA1c levels at the onset of T1D, and the average HbA1c levels after one and two years of disease duration. The subgroup A1 had the lowest initial HbA1c values, while the subgroup C had the highest initial HbA1c values. Cytokine levels (including TNF-α, IL-35, IL-4, IL-10, IL-18, and IL-12) were measured in all study participants. Our data analysis showed that subgroup A1 was characterized by significantly higher levels of IL-35 and IL-10 compared to all other groups, and significantly higher levels of IL-4 compared to group B. Additionally, a comparative analysis of cytokine levels between the groups of diabetic patients and healthy controls demonstrated that subgroup A1 had significantly higher levels of anti-inflammatory cytokines. The lipid profile was also significantly better in subgroup A1 compared to all other patient groups. Based on our findings, it appears that an inflammatory process, characterized by an imbalance between the pro- and anti-inflammatory cytokines, is associated with poor glycemic control at the onset of diabetes and during the first year of disease duration. These findings also suggest that both metabolic memory and inflammation contribute to the abnormal lipid profile in patients with type 1 diabetes.

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Potentials of bone marrow cells-derived from naïve or diabetic mice in autoimmune type 1 diabetes: immunomodulatory, anti-inflammatory, anti hyperglycemic, and antioxidative

Gomaa,

Nassef,

Hafez

2024

Endocrine

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Background: The scarcity of transplanted human islet tissue and the requirement for immunosuppressive drugs to prevent the rejection of allogeneic grafts have hindered the treatment of autoimmune type 1 diabetes mellitus (T1DM) through islet transplantation. However, there is hope in adoptively transferred bone marrow cells (BMCs) therapy, which has emerged as a propitious pathway for forthcoming medications. BMCs have the potential to significantly impact both replacement and regenerative therapies for a range of disorders, including diabetes mellitus, and have demonstrated anti-diabetic effects. Aim: The main goal of this study is to evaluate the effectiveness of adoptively transferred bone marrow cells derived from either naïve mice (nBMCs) or diabetic mice (dBMCs) in treating a T1DM mice model. Methods: Male Swiss albino mice were starved for 16 h and then injected with streptozotocin (STZ) at a dose of 40 mg/kg body weight for 5 consecutive days to induce T1DM. After 14 days, the diabetic mice were distributed into four groups. The first group served as a diabetic control treated with sodium citrate buffer, while the other three groups were treated for two weeks, respectively, with insulin (subcutaneously at a dose of 8 U/kg/day), nBMCs (intravenously at a dose of 1 × 106 cells/mouse/once), and dBMCs (intravenously at a dose of 1 × 106 cells/mouse/once). Results: It is worth noting that administering adoptively transferred nBMCs or adoptively transferred dBMCs to STZ-induced T1DM mice resulted in a significant amelioration in glycemic condition, accompanied by a considerable reduction in the level of blood glucose and glycosylated hemoglobin % (HbA1C %), ultimately restoring serum insulin levels to their initial state in control mice. Administering nBMCs or dBMCs to STZ-induced T1DM mice led to a remarkable decrease in levels of inflammatory cytokine markers in the serum, including interferon-γ (INF-γ), tumor necrosis factor- α (TNF-α), tumor growth factor-β (TGF-β), interleukin-1 β (L-1β), interlekin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10). Additionally, STZ-induced T1DM mice, when treated with nBMCs or dBMCs, experienced a notable rise in total immunoglobulin (Ig) level. Furthermore, there was a significant reduction in the levels of islet cell autoantibodies (ICA) and insulin autoantibodies (IAA). Furthermore, the serum of STZ-induced T1DM mice showed a significant increase in Zinc transporter 8 antigen protein (ZnT8), islet antigen 2 protein (IA-2), and glutamic acid decarboxylase antigen protein (GAD) levels. Interestingly, the administration of nBMCs or dBMCs resulted in a heightened expression of IA-2 protein in STZ-induced T1DM mice treated with nBMCs or dBMCs. Furthermore, the level of malondialdehyde (MDA) was increased, while the levels of catalase (CAT) and superoxide dismutase (SOD) were decreased in non-treated STZ-induced T1DM mice. However, when nBMCs or dBMCs were administered to STZ-induced T1DM mice, it had a significant impact on reducing oxidative stress. This was accomplished by reducing the levels of MDA in the serum and enhancing the activities of enzymatic antioxidants like CAT and SOD. STZ-induced T1DM mice displayed a significant elevation in the levels of liver enzymes ALT and AST, as well as heightened levels of creatinine and urea. Considering the crucial roles of the liver and kidney in metabolism and excretion, this research further examined the effects of administering nBMCs or dBMCs to STZ-induced T1DM mice. Notably, the administration of these cells alleviated the observed effects. Conclusion: The present study suggests that utilizing adoptively transferred nBMCs or adoptively transferred dBMCs in the treatment of T1DM led to noteworthy decreases in blood glucose levels, possibly attributed to their capacity to enhance insulin secretion and improve the performance of pancreatic islets. Additionally, BMCs may exert their beneficial effects on the pancreatic islets of diabetic mice through their immunomodulatory, antioxidant, anti-inflammatory, and anti-oxidative stress properties.

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The Relationship between Type 1 Diabetes Mellitus, TNF-α, and IL-10 Gene Expression

Cited by 14 publications

References 64 publications

Endowing Polyetheretherketone with Anti‐Infection and Immunomodulatory Properties through Guanidination Carbon Dots Modification to Promote Osseointegration in Diabetes with MRSA Infection

Endowing Polyetheretherketone with Anti‐Infection and Immunomodulatory Properties through Guanidination Carbon Dots Modification to Promote Osseointegration in Diabetes with MRSA Infection

The Impact of Metabolic Memory on Immune Profile in Young Patients with Uncomplicated Type 1 Diabetes

Potentials of bone marrow cells-derived from naïve or diabetic mice in autoimmune type 1 diabetes: immunomodulatory, anti-inflammatory, anti hyperglycemic, and antioxidative

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