Virulence factors of Staphylococcus aureus induce Erk-MAP kinase activation and c-Fos expression in S9 and 16HBE14o-human airway epithelial cells
Virulence factors of Staphylococcus aureus induce Erk-MAP kinase activation and c-Fos expression in S9 and 16HBE14o-human airway epithelial cells
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DOI：
10.1152/ajplung.90498.2008
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发表时间：
2009-03-01
影响因子：
4.9
通讯作者：
Hildebrandt, Jan-Peter
中科院分区：
文献类型：
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作者：
Below, Sabine;Konkel, Anne;Hildebrandt, Jan-Peter
Below S，Konkel A，Zeeck C，Muller C，科科勒C，Engelmann S，Hildebrandt JP.金黄色葡萄球菌的毒力因子诱导S9和16 HBE 140-人气道上皮细胞中Erk-MAP激酶活化和c-Fos表达。美国生理学杂志肺细胞分子生理学296：L470-L479，2009年。首次发表于2008年12月19日; doi：10.1152/ajplung.90498.2008。支气管上皮细胞对细菌定植的先天防御的一部分是调节盐、水和粘液的分泌以及涉及MAP激酶活化和早期基因表达改变的防御素和细胞因子。我们检测了两种不同类型的永生化人气道上皮细胞（S9，16 HBE 14 o-）在用来自稳定生长期的金黄色葡萄球菌培养上清液[光密度（OD）（540 nm）= 10]或重组S.金黄色葡萄球菌溶血素A和B（Hla，Hlb）。OD 10上清以浓度依赖性方式激活ERK型MAP激酶和c-Fos表达。Hla在S9细胞中诱导ERK激酶磷酸化，但在16 HBE 140-细胞中不诱导。在任一细胞类型中，Hlb诱导Erk活化。ERK型MAP激酶磷酸化的基础和刺激水平对Mek 1抑制剂PD-98059敏感，表明细菌产物激活了共调节IL-8诱导和分泌的整个信号级联。在S9细胞中，OD 10上清、Hla和Hlb增强c-Fos表达，而16 HBE 140-细胞对OD 10上清和Hlb有反应，但对Hla无反应。在S9细胞中，PD-98059抑制OD 10上清液、Hla或Hlb引起的c-Fos上调，表明c-Fos表达需要Erk型MAP激酶的激活。在16 HBE 14 o-细胞中，PD-98059对OD_（10）上清诱导的c-Fos表达敏感，而对Hlb诱导的c-Fos表达不敏感。这表明除了Hla或Hlb之外的OD 10上清液的成分在16 HBE 140-细胞中激活Erk型MAP激酶，并且除了Erk型MAP激酶之外的其他细胞内信号传导系统有助于Hlb介导的c-Fos调节。因此，细菌因子与气道上皮细胞的相互作用可能是高度细胞类型特异性的。
Below S, Konkel A, Zeeck C, Muller C, Kohler C, Engelmann S, Hildebrandt JP. Virulence factors of Staphylococcus aureus induce Erk-MAP kinase activation and c-Fos expression in S9 and 16HBE14o- human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 296: L470-L479, 2009. First published December 19, 2008; doi: 10.1152/ajplung.90498.2008.-Part of the innate defense of bronchial epithelia against bacterial colonization is regulated secretion of salt, water, and mucus as well as defensins and cytokines involving MAP kinase activation and alterations in early gene expression. We tested two different types of immortalized human airway epithelial cells (S9, 16HBE14o-) for activation of Erk-type MAP kinases and for expression of c-Fos on treatment with Staphylococcus aureus culture supernatants from the stationary growth phase [optical density (OD)(540nm) = 10] or with recombinant S. aureus hemolysins A and B (Hla, Hlb). OD10 supernatants activated Erk-type MAP kinases and c-Fos expression in a concentration-dependent manner. Hla induced Erk-type kinase phosphorylation in S9 but not in 16HBE14o- cells. Hlb induced Erk activation in either cell type. Basal and stimulated levels of Erk-type MAP kinase phosphorylation were sensitive to the Mek1 inhibitor PD-98059, indicating that the bacterial products activated the entire signaling cascade that coregulates IL-8 induction and secretion. While c-Fos expression was enhanced by OD10 supernatants, Hla, and Hlb in S9 cells, 16HBE14o- cells responded to OD10 supernatant and Hlb but not to Hla. In S9 cells, PD-98059 suppressed c-Fos upregulation by OD10 supernatant, Hla, or Hlb, indicating that c-Fos expression requires activation of Erk-type MAP kinases. In 16HBE14o- cells, however, c-Fos expression by OD10 supernatant was sensitive to PD-98059, while that induced by Hlb was not. This indicates that ingredients of OD10 supernatants other than Hla or Hlb are activating Erk-type MAP kinases in 16HBE14o- cells and that other intracellular signaling systems apart from Erk-type MAP kinases contribute to Hlb-mediated regulation of c-Fos. Thus interaction of bacterial factors with airway epithelial cells may be highly cell type specific.