Differential modulation of the induction of inflammatory mediators by antibiotics in mouse macrophages in response to viable Gram-positive and Gram-negative bacteria

Differential modulation of the induction of inflammatory mediators by antibiotics in mouse macrophages in response to viable Gram-positive and Gram-negative bacteria
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DOI:
10.1179/096805103225001422
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发表时间:
2003-01-01
期刊:
JOURNAL OF ENDOTOXIN RESEARCH
影响因子:
--
通讯作者:
Morrison, DC
Morrison, DC
中科院分区:
其他
文献类型:
--
作者:
Cui, W;Lei, MG;Morrison, DC

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我们研究了β -内酰胺类抗生素对小鼠腹腔巨噬细胞与大肠杆菌或金黄色葡萄球菌共培养后tnf - α和NOS产生的影响。头孢他啶和氨曲南增强大肠杆菌刺激巨噬细胞tnf - α分泌;然而,imipenem。不会改变大肠杆菌处理的巨噬细胞中TNF-a的动力学或大小。金黄色葡萄球菌与巨噬细胞共培养的类似处理显著改变了tnf - α反应的特征,其特征是相对于未处理的金黄色葡萄球菌,tnf - α明显提前达到峰值。所有抗生素均增加了大肠杆菌诱导的NOS的mRNA和蛋白表达。这些抗生素显著降低了金黄色葡萄球菌诱导的NOS RNA水平。头孢他啶和阿唑南都有。与亚胺培南处理的细菌的低水平LPS释放相比,大肠杆菌的LPS释放增加,这与观察到的tnf - α释放差异一致。所有三种抗生素与金黄色葡萄球菌孵育在早期时间点上清液中检测到的细胞壁成分蛋白A水平同样增加,表明微生物裂解。与此同时,金黄色葡萄球菌培养上清与抗生素孵育2小时可增强tnf - α的释放。这些结果表明,不同的细胞机制有助于抗生素介导的小鼠巨噬细胞对大肠杆菌和金黄色葡萄球菌的TNF-a和NOS分泌的调节。
We have investigated effects of beta-lactam antibiotics on TNF-alpha, and NOS production from mouse peritoneal macrophages following co-culture with Escherichia coli or Staphylococcus aureus bacteria. Ceftazidime and aztreonam enhanced TNF-alpha secretion from macrophages stimulated with E coli; however, imipenem. does not alter either the kinetics or magnitude of TNF-a in E coli-treated macrophages. Similar treatments with S. aureus co-cultured with macrophages markedly altered profiles of TNF-alpha response characterized by apparent early TNF-alpha peak relative to untreated S. aureus. All antibiotics increased E coli-induced NOS expression as assessed by both mRNA and protein. These same antibiotics significantly reduced S. aureus-induced NOS levels of RNA. Both ceftazidime and aztreonam. enhanced LPS release from E coli in comparison to low-level LPS release from imipenem-treated bacteria, consistent with observed differences in TNF-alpha release. Incubation of all three antibiotics with S, aureus similarly increased levels of the cell wall constituent protein A detected in supernatants at early time points indicating microbial lysis. In parallel, S. aureus culture supernatants from 2-h incubation with antibiotics enhanced TNF-alpha release. These results indicate that different cellular mechanisms contribute to antibiotic-mediated regulation of TNF-a and NOS secretion in mouse macrophages in response to E coli versus S. aureus.