One-way synergistic effect of low superantigen concentrations on lipopolysaccharide-induced cytokine production
One-way synergistic effect of low superantigen concentrations on lipopolysaccharide-induced cytokine production
复制标题
DOI：
10.1089/jir.1997.17.229
复制
发表时间：
1997-04-01
影响因子：
2.3
通讯作者：
Rink, L
中科院分区：
文献类型：
--
作者：
Luhm, J;Kirchner, H;Rink, L
革兰氏阴性菌的脂多糖（LPS）和革兰氏阳性菌的超抗原是脓毒症和感染性休克的主要原因，症状主要由内源性介质尤其是细胞因子的释放引发。近年来，越来越多的证据表明，两种细菌共感染引起的混合性脓毒症具有临床相关性，因此，我们建立了体外混合脓毒症模型，通过ELISA和RT-PCR研究了不同剂量的超抗原联合不同浓度的LPS对人PBMCs细胞因子产生的影响。体内低浓度的超抗原毒性休克综合征毒素-1 （TSST-1）协同增强LPS诱导的干扰素- γ (ifn - γ)、白细胞介素-1 β (IL-1 β)、IL-6和IL-10的产生，但低浓度的LPS没有类似的作用。不同抑制剂的信号转导研究表明，这种单向协同作用是由cAMP和PIP2信号通路之间的相互作用引起的。此外，我们的研究结果支持这种相互作用是LPS和超级抗原信号转导通路的一个重要交叉点，这似乎主要由ifn - γ和PGE-2调节。在混合性脓毒症的发生过程中发现额外的交叉点及其选择性影响可能导致革兰氏阴性和革兰氏阳性脓毒症的相同治疗。
Lipopolysaccharides (LPS) of gram-negative bacteria and superantigens of gram-positive bacteria are among the main causes of sepsis and septic shock, Symptoms are initiated primarily by the release of endogenous mediators, especially cytokines, In the last few years, increasing evidence for the clinical relevance of mixed sepsis caused by coinfections with both types of bacteria has been found, Therefore, we developed an in vitro mixed sepsis model investigating the effect of different superantigen doses, in combination with different LPS concentrations, on cytokine production in human PBMCs using ELISA and RT-PCR, Low, in vivo relevant concentrations of the superantigen toxic shock syndrome toxin-1 (TSST-1) synergistically enhance LPS-induced production of interferon-gamma (IFN-gamma) interleukin-1 beta (IL-1 beta), IL-6, and IL-10, but low LPS has no comparable effect, Signal transduction studies with different inhibitors suggest that this one-way synergism is caused by an interaction between the cAMP and the PIP2 signaling pathway, Furthermore, our findings support the idea that this interaction is one important crossover point of signal transduction pathways by LPS and superantigens, which seems to be predominantly regulated by IFN-gamma and PGE-2. The identification of additional crossover points in the genesis of a mixed sepsis and their selective influence could lead to identical treatment of both gram-negative and gram-positive sepsis.