High glucose concentrations induce TNF-α production through the down-regulation of CD33 in primary human monocytes.
High glucose concentrations induce TNF-α production through the down-regulation of CD33 in primary human monocytes.
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DOI：
10.1186/1471-2172-13-19
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发表时间：
2012-04-14
期刊：
影响因子：
3
通讯作者：
Torres M
中科院分区：
文献类型：
--
作者：
Gonzalez Y;Herrera MT;Soldevila G;Garcia-Garcia L;Fabián G;Pérez-Armendariz EM;Bobadilla K;Guzmán-Beltrán S;Sada E;Torres M
CD 33是一种膜受体，含有凝集素结构域和细胞质免疫受体酪氨酸基抑制基序（ITIM），能够抑制细胞因子的产生。CD 33由单核细胞表达，并且CD 33的表达减少与炎性细胞因子（例如IL-1β、TNF-α和IL-8）的产生增加相关。然而，CD 33在与高血糖症和糖尿病相关的炎症中的作用尚不清楚。因此，我们研究了2型糖尿病患者新鲜分离的单核细胞中CD 33表达和炎症细胞因子分泌。为了评估高血糖症的影响，将来自健康供体的单核细胞与不同葡萄糖浓度（15-50 mmol/l D-葡萄糖）培养，并评估CD 33表达和炎性细胞因子产生。还评估了细胞因子信号传导蛋白-3（SOCS-3）抑制因子的表达和活性氧（ROS）的产生，以解决涉及CD 33下调的细胞机制。2型糖尿病患者的单核细胞中CD 33表达显著降低，与健康供体相比，患者血浆中检测到较高水平的TNF-α、IL-8和IL-12 p70。在高糖条件下，健康供体单核细胞中CD 33蛋白和mRNA表达显著降低，而自发TNF-α分泌和SOCS-3 mRNA表达增加。此外，当单核细胞用抗氧化剂α-生育酚处理并在高糖条件下培养时，CD 33的下调和TNF-α产生的增加被阻止。我们的研究结果表明，高血糖下调CD 33的表达，并触发外周血单核细胞自发分泌TNF-α。这种现象涉及ROS的产生和SOCS-3的上调。这些观察结果支持血糖控制对于维持先天免疫功能的重要性，并表明CD 33参与与2型糖尿病相关的炎症特征。
CD33 is a membrane receptor containing a lectin domain and a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) that is able to inhibit cytokine production. CD33 is expressed by monocytes, and reduced expression of CD33 correlates with augmented production of inflammatory cytokines, such as IL-1β, TNF-α, and IL-8. However, the role of CD33 in the inflammation associated with hyperglycemia and diabetes is unknown. Therefore, we studied CD33 expression and inflammatory cytokine secretion in freshly isolated monocytes from patients with type 2 diabetes. To evaluate the effects of hyperglycemia, monocytes from healthy donors were cultured with different glucose concentrations (15-50 mmol/l D-glucose), and CD33 expression and inflammatory cytokine production were assessed. The expression of suppressor of cytokine signaling protein-3 (SOCS-3) and the generation of reactive oxygen species (ROS) were also evaluated to address the cellular mechanisms involved in the down-regulation of CD33. CD33 expression was significantly decreased in monocytes from patients with type 2 diabetes, and higher levels of TNF-α, IL-8 and IL-12p70 were detected in the plasma of patients compared to healthy donors. Under high glucose conditions, CD33 protein and mRNA expression was significantly decreased, whereas spontaneous TNF-α secretion and SOCS-3 mRNA expression were increased in monocytes from healthy donors. Furthermore, the down-regulation of CD33 and increase in TNF-α production were prevented when monocytes were treated with the antioxidant α-tocopherol and cultured under high glucose conditions. Our results suggest that hyperglycemia down-regulates CD33 expression and triggers the spontaneous secretion of TNF-α by peripheral monocytes. This phenomenon involves the generation of ROS and the up-regulation of SOCS-3. These observations support the importance of blood glucose control for maintaining innate immune function and suggest the participation of CD33 in the inflammatory profile associated with type 2 diabetes.
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影响因子：
7.7
作者：
Duncan, BB;Schmidt, MI;Heiss, G
通讯作者：
Heiss, G
影响因子：
16.2
作者：
Ghanim H;Abuaysheh S;Sia CL;Korzeniewski K;Chaudhuri A;Fernandez-Real JM;Dandona P
通讯作者：
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影响因子：
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通讯作者：
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作者：
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通讯作者：
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