Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus
Aim: To analyze indoleamine 2,3-dioxygenase (IDO) production in the cell culture supernatant of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from type 2 DM (T2DM) patients and investigate IDO’s association to pro- and anti-inflammatory cytokines. Subjects and method...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
SAGE Publishing
2020-12-01
|
Series: | International Journal of Tryptophan Research |
Online Access: | https://doi.org/10.1177/1178646920978236 |
id |
doaj-6458c05e249d4e55ac7fe07a42dc764f |
---|---|
record_format |
Article |
spelling |
doaj-6458c05e249d4e55ac7fe07a42dc764f2020-12-10T00:03:42ZengSAGE PublishingInternational Journal of Tryptophan Research1178-64692020-12-011310.1177/1178646920978236Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes MellitusRona Kartika0Heri Wibowo1Dyah Purnamasari2Saraswati Pradipta3Rahma A Larasati4Master’s Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta IndonesiaDepartment of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaDivision of Metabolic Endocrinology and Diabetes, Department of Internal Medicine, Faculty of Medicine, Cipto Mangunkusumo National Public Hospital, Universitas Indonesia, Jakarta, IndonesiaMaster’s Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta IndonesiaDepartment of Biomedicines, Faculty of Medicine, Universitas Muhammadiyah Jakarta, Jakarta, IndonesiaAim: To analyze indoleamine 2,3-dioxygenase (IDO) production in the cell culture supernatant of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from type 2 DM (T2DM) patients and investigate IDO’s association to pro- and anti-inflammatory cytokines. Subjects and methods: PBMC samples were collected from 21 T2DM patients and 17 normoglycemic participants, then stimulated with PHA for 3 days. Cytokine and IDO concentrations were measured in the PBMC culture supernatants. In vitro production of TNF-α, IL-6, interferon-γ, and IL-10 were measured using multiplex immunoassay. IDO concentration was assessed using ELISA. To assess how PHA stimulation altered IDO production and to minimize the unstimulated baseline effect of T2DM, we subtracted the PHA-stimulated IDO concentration from the unstimulated one. IBM SPSS version 23 was used for statistical analysis. Results: The IDO concentrations in the PBMC culture supernatants were significantly higher in T2DM patients regardless of whether they were unstimulated ( P < .001) or PHA-stimulated ( P = .012). Reduced IDO production was observed in 52.8% of T2DM patients and was associated with older age and lower interferon-γ levels. Conversely, 42.8% of T2DM patients showed increased IDO concentrations, which were correlated with the IL-6/IL-10 ratio ( r = 0.683, P = .021) and interferon-γ/IL-10 ratio ( r = 0.517, P = .077). Conclusion: The interferon-γ level was reduced in the PBMC culture supernatant of T2DM patients with reduced IDO production. Reduced IDO production in T2DM patients following PHA stimulation was associated with older age and, notably, higher baseline IDO concentrations. Since IDO is primarily produced by dendritic cells, reduced IDO production after PHA stimulation may indicate dendritic cell dysfunction.https://doi.org/10.1177/1178646920978236 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rona Kartika Heri Wibowo Dyah Purnamasari Saraswati Pradipta Rahma A Larasati |
spellingShingle |
Rona Kartika Heri Wibowo Dyah Purnamasari Saraswati Pradipta Rahma A Larasati Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus International Journal of Tryptophan Research |
author_facet |
Rona Kartika Heri Wibowo Dyah Purnamasari Saraswati Pradipta Rahma A Larasati |
author_sort |
Rona Kartika |
title |
Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus |
title_short |
Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus |
title_full |
Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus |
title_fullStr |
Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus |
title_full_unstemmed |
Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus |
title_sort |
altered indoleamine 2,3-dioxygenase production and its association to inflammatory cytokines in peripheral blood mononuclear cells culture of type 2 diabetes mellitus |
publisher |
SAGE Publishing |
series |
International Journal of Tryptophan Research |
issn |
1178-6469 |
publishDate |
2020-12-01 |
description |
Aim: To analyze indoleamine 2,3-dioxygenase (IDO) production in the cell culture supernatant of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from type 2 DM (T2DM) patients and investigate IDO’s association to pro- and anti-inflammatory cytokines. Subjects and methods: PBMC samples were collected from 21 T2DM patients and 17 normoglycemic participants, then stimulated with PHA for 3 days. Cytokine and IDO concentrations were measured in the PBMC culture supernatants. In vitro production of TNF-α, IL-6, interferon-γ, and IL-10 were measured using multiplex immunoassay. IDO concentration was assessed using ELISA. To assess how PHA stimulation altered IDO production and to minimize the unstimulated baseline effect of T2DM, we subtracted the PHA-stimulated IDO concentration from the unstimulated one. IBM SPSS version 23 was used for statistical analysis. Results: The IDO concentrations in the PBMC culture supernatants were significantly higher in T2DM patients regardless of whether they were unstimulated ( P < .001) or PHA-stimulated ( P = .012). Reduced IDO production was observed in 52.8% of T2DM patients and was associated with older age and lower interferon-γ levels. Conversely, 42.8% of T2DM patients showed increased IDO concentrations, which were correlated with the IL-6/IL-10 ratio ( r = 0.683, P = .021) and interferon-γ/IL-10 ratio ( r = 0.517, P = .077). Conclusion: The interferon-γ level was reduced in the PBMC culture supernatant of T2DM patients with reduced IDO production. Reduced IDO production in T2DM patients following PHA stimulation was associated with older age and, notably, higher baseline IDO concentrations. Since IDO is primarily produced by dendritic cells, reduced IDO production after PHA stimulation may indicate dendritic cell dysfunction. |
url |
https://doi.org/10.1177/1178646920978236 |
work_keys_str_mv |
AT ronakartika alteredindoleamine23dioxygenaseproductionanditsassociationtoinflammatorycytokinesinperipheralbloodmononuclearcellscultureoftype2diabetesmellitus AT heriwibowo alteredindoleamine23dioxygenaseproductionanditsassociationtoinflammatorycytokinesinperipheralbloodmononuclearcellscultureoftype2diabetesmellitus AT dyahpurnamasari alteredindoleamine23dioxygenaseproductionanditsassociationtoinflammatorycytokinesinperipheralbloodmononuclearcellscultureoftype2diabetesmellitus AT saraswatipradipta alteredindoleamine23dioxygenaseproductionanditsassociationtoinflammatorycytokinesinperipheralbloodmononuclearcellscultureoftype2diabetesmellitus AT rahmaalarasati alteredindoleamine23dioxygenaseproductionanditsassociationtoinflammatorycytokinesinperipheralbloodmononuclearcellscultureoftype2diabetesmellitus |
_version_ |
1724387747507994624 |