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首页> 外文期刊>Infection and immunity >Role of MyD88 in Diminished Tumor Necrosis Factor Alpha Production by Newborn Mononuclear Cells in Response to Lipopolysaccharide
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Role of MyD88 in Diminished Tumor Necrosis Factor Alpha Production by Newborn Mononuclear Cells in Response to Lipopolysaccharide

机译：MyD88在新生儿单核细胞对脂多糖反应中减少的肿瘤坏死因子α产生中的作用。

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Human newborns are more susceptible than adults to infection by gram-negative bacteria. We hypothesized that this susceptibility may be associated with a decreased response by leukocytes to lipopolysaccharide (LPS). In this study, we compared LPS-induced secretion of tumor necrosis factor alpha (TNF-α) by mononuclear cells (MNC) from adult peripheral blood and newborn umbilical cord blood in vitro and attempted to determine the mechanisms involved in its regulation. At a high concentration of LPS (10 ng/ml) and in the presence of autologous plasma, MNC from adults and newborns secreted similar amounts of TNF-α. However, in the absence of plasma, MNC from newborns secreted significantly less TNF-α compared to MNC from adults. Moreover, at a low concentration of LPS (0.1 ng/ml) and in the presence of plasma, TNF-α secretion was significantly lower for newborn MNC compared to adult MNC. Adults and newborns had similar numbers of CD14 and Toll-like receptor 4 (TLR-4)-positive cells as measured by flow cytometry. However, the intensity of the CD14 marker was greater for adult than for newborn cells. Incubation of cells with LPS led to an increase in CD14 and TLR-4 intensity for adult cells but not for newborn cells. The effect of LPS stimulation of adult or newborn cells was similar for ERK, p38, and IκBα phosphorylation, as well as IκBα degradation. Finally, we assessed levels of the TLR-4 adapter protein, the myeloid differentiation antigen 88 (MyD88). We found a direct relation between adult and newborn TNF-α secretion and MyD88, which was significantly decreased in newborn monocytes. Since TLR-4 signals intracellularly through the adapter protein, MyD88, we hypothesize that MyD88-dependent factors are responsible for delayed and decreased TNF-α secretion in newborn monocytes.
机译：与新生儿相比，人类新生儿更容易受到革兰氏阴性细菌的感染。我们假设这种敏感性可能与白细胞对脂多糖（LPS）的反应降低有关。在这项研究中，我们比较了成人外周血和新生儿脐带血中单核细胞（MNC）对LPS诱导的肿瘤坏死因子α（TNF-α）的分泌，并试图确定其调控机制。在高浓度LPS（10 ng / ml）和自体血浆存在的情况下，成人和新生儿的MNC分泌相似量的TNF-α。但是，在没有血浆的情况下，新生儿的MNC分泌的TNF-α明显少于成人的MNC。此外，与成人MNC相比，在低浓度LPS（0.1 ng / ml）和存在血浆的情况下，新生MNC的TNF-α分泌显着降低。通过流式细胞术测量，成人和新生儿的CD14和Toll样受体4（TLR-4）阳性细胞数量相似。但是，成人的CD14标记强度要高于新生细胞。用LPS孵育细胞会导致成年细胞的CD14和TLR-4强度增加，而新生细胞却没有。 LPS刺激对成年或新生细胞的作用在ERK，p38和IκBα磷酸化以及IκBα降解方面相似。最后，我们评估了TLR-4衔接蛋白，髓样分化抗原88（MyD88）的水平。我们发现成人和新生儿TNF-α分泌与MyD88之间存在直接关系，而新生儿单核细胞中MyD88的分泌显着减少。由于TLR-4通过衔接蛋白MyD88在细胞内发出信号，因此我们推测MyD88依赖性因子是导致新生儿单核细胞中TNF-α分泌延迟和减少的原因。

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