Cellular Advanced Glycation End Products Aggravate the Immune Response in Mononuclear Cells from Patients with Type 1 Diabetes
Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune response mediated islet beta cells destruction. However, the mechanisms that cause immune response in TIDM are still under investigation. Therefore, the goal of this study was to investigate the role of adva...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2024-02-01
|
| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/29/2/10.31083/j.fbl2902085 |
| _version_ | 1797290411170988032 |
|---|---|
| author | Liang Yang Yuxuan Qian Shixin Lei Dongping Sun |
| author_facet | Liang Yang Yuxuan Qian Shixin Lei Dongping Sun |
| author_sort | Liang Yang |
| collection | DOAJ |
| description | Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune response mediated islet beta cells destruction. However, the mechanisms that cause immune response in TIDM are still under investigation. Therefore, the goal of this study was to investigate the role of advanced glycation end products (AGEs) in the regulation of the immune response in peripheral blood mononuclear cells (PBMCs) from patients with T1DM. Methods: PBMCs isolated from T1DM patients and control subjects were used in the current study. Cytokines, AGEs related to glyoxalase 1 (GLO1), methylglyoxal (MG)-derived AGEs were assessed longitudinally. Results: The results of published T1DM PBMC microarray datasets using random-effects meta-analysis models revealed immune responses in the PBMCs of patients with T1DM compared with control subjects. Moreover, the activity of GLO1, which is the key MG-metabolizing enzyme, was significantly reduced in PBMCs from T1DM patients. We confirmed that, compared to the control subjects, GLO1 expression and activity were markedly decreased and MG-derived AGEs were significantly accumulated in the PBMCs from T1DM patients. In addition, phytohemagglutinin stimulated the secretion of tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) was positively correlated with the accumulation of cellular AGEs. Therefore, the exposure of PBMCs from control subjects to MG and a GLO1 inhibitor enhanced the accumulation of cellular MG-derived AGEs and the secretion of TNF-α and IFN-γ. Conclusions: The results of this study showed that the accumulation of cellular AGEs causes a decline in the immune response of patients with T1DM. |
| first_indexed | 2024-03-07T19:21:58Z |
| format | Article |
| id | doaj.art-80789e09ad9e4c258d3786714ae2f924 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-07T19:21:58Z |
| publishDate | 2024-02-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-80789e09ad9e4c258d3786714ae2f9242024-02-29T09:53:15ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-02-012928510.31083/j.fbl2902085S2768-6701(23)01143-7Cellular Advanced Glycation End Products Aggravate the Immune Response in Mononuclear Cells from Patients with Type 1 DiabetesLiang Yang0Yuxuan Qian1Shixin Lei2Dongping Sun3School of Basic Medical Science, Gansu Medical College, 744000 Pingliang, Gansu, ChinaDepartment of Biology, School of Arts & Sciences, University of Rochester, Rochester, NY 14627, USASchool of Basic Medical Science, Gansu Medical College, 744000 Pingliang, Gansu, ChinaDepartment of Clinical Medicine, The Affiliated Hospital of Gansu Medical College, 744000 Pingliang, Gansu, ChinaBackground: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune response mediated islet beta cells destruction. However, the mechanisms that cause immune response in TIDM are still under investigation. Therefore, the goal of this study was to investigate the role of advanced glycation end products (AGEs) in the regulation of the immune response in peripheral blood mononuclear cells (PBMCs) from patients with T1DM. Methods: PBMCs isolated from T1DM patients and control subjects were used in the current study. Cytokines, AGEs related to glyoxalase 1 (GLO1), methylglyoxal (MG)-derived AGEs were assessed longitudinally. Results: The results of published T1DM PBMC microarray datasets using random-effects meta-analysis models revealed immune responses in the PBMCs of patients with T1DM compared with control subjects. Moreover, the activity of GLO1, which is the key MG-metabolizing enzyme, was significantly reduced in PBMCs from T1DM patients. We confirmed that, compared to the control subjects, GLO1 expression and activity were markedly decreased and MG-derived AGEs were significantly accumulated in the PBMCs from T1DM patients. In addition, phytohemagglutinin stimulated the secretion of tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) was positively correlated with the accumulation of cellular AGEs. Therefore, the exposure of PBMCs from control subjects to MG and a GLO1 inhibitor enhanced the accumulation of cellular MG-derived AGEs and the secretion of TNF-α and IFN-γ. Conclusions: The results of this study showed that the accumulation of cellular AGEs causes a decline in the immune response of patients with T1DM.https://www.imrpress.com/journal/FBL/29/2/10.31083/j.fbl2902085type 1 diabetesperipheral blood mononuclear cellspro-inflammatory cytokinesadvanced glycation end products |
| spellingShingle | Liang Yang Yuxuan Qian Shixin Lei Dongping Sun Cellular Advanced Glycation End Products Aggravate the Immune Response in Mononuclear Cells from Patients with Type 1 Diabetes Frontiers in Bioscience-Landmark type 1 diabetes peripheral blood mononuclear cells pro-inflammatory cytokines advanced glycation end products |
| title | Cellular Advanced Glycation End Products Aggravate the Immune Response in Mononuclear Cells from Patients with Type 1 Diabetes |
| title_full | Cellular Advanced Glycation End Products Aggravate the Immune Response in Mononuclear Cells from Patients with Type 1 Diabetes |
| title_fullStr | Cellular Advanced Glycation End Products Aggravate the Immune Response in Mononuclear Cells from Patients with Type 1 Diabetes |
| title_full_unstemmed | Cellular Advanced Glycation End Products Aggravate the Immune Response in Mononuclear Cells from Patients with Type 1 Diabetes |
| title_short | Cellular Advanced Glycation End Products Aggravate the Immune Response in Mononuclear Cells from Patients with Type 1 Diabetes |
| title_sort | cellular advanced glycation end products aggravate the immune response in mononuclear cells from patients with type 1 diabetes |
| topic | type 1 diabetes peripheral blood mononuclear cells pro-inflammatory cytokines advanced glycation end products |
| url | https://www.imrpress.com/journal/FBL/29/2/10.31083/j.fbl2902085 |
| work_keys_str_mv | AT liangyang cellularadvancedglycationendproductsaggravatetheimmuneresponseinmononuclearcellsfrompatientswithtype1diabetes AT yuxuanqian cellularadvancedglycationendproductsaggravatetheimmuneresponseinmononuclearcellsfrompatientswithtype1diabetes AT shixinlei cellularadvancedglycationendproductsaggravatetheimmuneresponseinmononuclearcellsfrompatientswithtype1diabetes AT dongpingsun cellularadvancedglycationendproductsaggravatetheimmuneresponseinmononuclearcellsfrompatientswithtype1diabetes |