Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus.
Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus.
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DOI：
10.1177/1178646920978236
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Larasati RA
中科院分区：
文献类型：
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作者：
Kartika R;Wibowo H;Purnamasari D;Pradipta S;Larasati RA
分析2型糖尿病（T2 DM）患者植物血凝素（PHA）刺激的外周血单个核细胞（PBMCs）细胞培养上清液中吲哚胺2，3-双加氧酶（IDO）的产生，并研究IDO与促炎和抗炎细胞因子的相关性。从21名T2 DM患者和17名血糖正常的参与者收集PBMC样品，然后用PHA刺激3天。在PBMC培养上清液中测量细胞因子和IDO浓度。采用多重免疫测定法测定TNF-α、IL-6、IFN-γ和IL-10的体外产生。使用ELISA评估IDO浓度。为了评估PHA刺激如何改变IDO产生并使T2 DM的未刺激基线效应最小化，我们从未刺激的IDO浓度中减去PHA刺激的IDO浓度。使用IBM SPSS 23版进行统计分析。PBMC培养上清液中的IDO浓度在T2 DM患者中显著更高，无论他们是未经刺激的（P <0.001）还是PHA刺激的（P = 0.012）。在52.8%的T2 DM患者中观察到IDO产生减少，并且与年龄较大和干扰素-γ水平较低相关。相反，42.8%的T2 DM患者显示IDO浓度升高，其与IL-6/IL-10比值（r = 0.683，P = 0.021）和干扰素-γ/IL-10比值（r = 0.517，P = 0.077）相关。IDO产生减少的T2 DM患者PBMC培养上清中IFN-γ水平降低。PHA刺激后T2 DM患者IDO产生减少与年龄较大相关，尤其是基线IDO浓度较高。由于IDO主要由树突细胞产生，因此PHA刺激后IDO产生减少可能表明树突细胞功能障碍。
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. 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. 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). 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.