Low-dose lipopolysaccharide modifies the production of IL-12 by dendritic cells in response to various cytokines.
Low-dose lipopolysaccharide modifies the production of IL-12 by dendritic cells in response to various cytokines.
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DOI：
10.3960/jslrt.46.31
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发表时间：
2006-03
期刊：
影响因子：
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通讯作者：
Yusuke Saito;Y. Yanagawa;Kazuhiro Kikuchi;Norifumi Iijima;K. Iwabuchi;K. Onoé
中科院分区：
文献类型：
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作者：
Yusuke Saito;Y. Yanagawa;Kazuhiro Kikuchi;Norifumi Iijima;K. Iwabuchi;K. Onoé
树突状细胞（DC）的激活是由细胞因子触发的，包括肿瘤坏死因子(TNF)- α和微生物成分，包括脂多糖（LPS）。在感染初期，微生物成分呈低浓度存在。为了确定感染初期低剂量微生物成分在DC激活中的作用，我们检测了低剂量LPS对细胞因子诱导的DC成熟和功能的影响。低剂量LPS （1 ng/ml）处理树突状细胞仅对多种细胞因子(包括白细胞介素（IL)-1 β、tnf - α和干扰素(IFN)- γ）诱导的CD86和主要组织相容性复合体II类的表达产生叠加效应。单独il -1 β显著诱导dc中IL-12的产生，而tnf - α或ifn - γ诱导适度水平的IL-12产生。低剂量LPS （1 ng/ml）仅能轻微诱导IL-12的产生，对il -1 β诱导的IL-12产生有加性作用。相反，低剂量LPS协同增强tnf - α或ifn - γ诱导的IL-12产生。SB203580是一种p38 MAPK的特异性抑制剂，在不存在LPS或不存在LPS的情况下，都能显著抑制tnf - α或ifn - γ诱导的il -12的产生，但对il - β诱导的il -12的产生仅表现出适度的影响。这些发现表明，p38 MAPK通路对于tnf - α或ifn - γ联合低剂量LPS诱导的DC中IL-12的协同产生至关重要。
Dendritic cell (DC) activation is triggered by cytokines, including tumor necrosis factor (TNF)-alpha, and microbe components, including lipopolysaccharide (LPS). During the initial stage of infection, the microbe components appear to be present at low concentration. To determine the role of low-dose microbe-components in DC activation during the initial stage of infection, we examined the effects of low-dose LPS on cytokine-induced maturation and function of DCs. Low-dose LPS (1 ng/ml) treatment of DCs had only additive effects on the expression of CD86 and major histocompatibility complex class II induced by various cytokines, including interleukin (IL)-1beta, TNF-alpha and interferon (IFN)-gamma. IL-1beta alone significantly induced IL-12 production in DCs, whereas TNF-alpha or IFN-gamma induced modest levels of IL-12 production. When low-dose LPS (1 ng/ml), which only slightly induced IL-12 production, was added to the culture, only an additive effect was seen on IL-1beta-induced IL-12 production. In contrast, low-dose LPS synergistically enhanced TNF-alpha- or IFN-gamma-induced IL-12 production. SB203580, a specific inhibitor of p38 MAPK, markedly inhibited TNF-alpha- or IFN-gamma-induced IL-12-production either in the absence or presence of LPS, but showed only modest effects on IL-beta-induced IL-12-production. These findings suggest that the p38 MAPK pathway is essential for the synergistic IL-12 production induced by TNF-alpha- or IFN-gamma in combination with low-dose LPS in DC.