Induction of cytokine synthesis by flagella from gram-negative bacteria may be dependent on the activation or differentiation state of human monocytes
Induction of cytokine synthesis by flagella from gram-negative bacteria may be dependent on the activation or differentiation state of human monocytes
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DOI：
10.1128/iai.67.10.5176-5185.1999
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发表时间：
1999-10-01
影响因子：
3.1
通讯作者：
Mizel, SB
中科院分区：
文献类型：
--
作者：
Ciacci-Wooline, F;McDermott, PF;Mizel, SB
我们之前已经证明，沙门氏菌，而不是大肠杆菌或小肠结肠炎耶尔森氏菌，能刺激人前单核细胞系U38产生肿瘤坏死因子α(TNFα)。随后的分析表明，沙门氏菌的肿瘤坏死因子α诱导活性与鞭毛蛋白有关，鞭毛蛋白是革兰氏阴性细菌鞭毛的主要成分。在本研究中，我们探索了鞭毛沙门氏菌对U38细胞中肿瘤坏死因子α表达的明显特异性的基础，并将这一分析扩展到正常人外周血单核细胞(PBMC)。致病性大肠埃希菌E2348/69、肠结肠杆菌JB580和铜绿假单胞菌PAO1的鞭毛对U38细胞产生的肿瘤坏死因子α和白细胞介素1β的活性与鞭毛沙门氏菌相当。然而，当U38细胞在共刺激剂佛波醇13-肉豆蔻酸酯存在的情况下，用来自大肠杆菌、小肠结肠炎耶尔森菌和铜绿假单胞菌的鞭毛刺激这些细胞时，这些细胞的肿瘤坏死因子α的产生显著增加。这些发现与单核细胞的激活或分化状态可能对细胞对鞭毛刺激细胞因子合成的反应有实质性影响的假设是一致的。此外，这些结果表明，单核细胞中细胞因子的诱导可能是革兰氏阴性菌鞭毛的一种普遍特性。
We have previously demonstrated that salmonellae, but not Escherichia coli or Yersinia enterocolitica, stimulates tumor necrosis factor alpha (TNF alpha) production in the human promonocytic cell line U38. Subsequent analysis revealed that the TNF alpha-inducing activity of salmonellae was associated with flagellin, a major component of flagella from gram-negative bacteria. In the present study, we have explored the basis for the apparent specificity of action of Salmonella flagella on TNF alpha expression in U38 cells and have extended this analysis to normal human peripheral blood mononuclear cells (PBMC). Flagella from the enteropathogenic E. coli strain E2348/69, Y. enterocolitica JB580, and Pseudomonas aeruginosa PAO1, which did not induce significant levels of TNF alpha production in U38 cells, were as potent as Salmonella flagella in terms of TNF alpha and interleukin 1 beta activation in PBMC. However, TNF alpha production in U38 cells was greatly enhanced when these cells were stimulated with flagella from E. coli, Y. enterocolitica, and P. aeruginosa in the presence of a costimulant, phorbol 13-myristate acetate. These findings are consistent with the hypothesis that the activation or differentiation state of a monocyte may have a substantial effect on the cell's responsiveness to flagellum stimulation of cytokine synthesis. Furthermore, these results indicate that cytokine induction in monocytes may be a general property of flagella from gram-negative bacteria.