Relation of exaggerated cytokine responses of CF airway epithelial cells to PAO1 adherence.

Relation of exaggerated cytokine responses of CF airway epithelial cells to PAO1 adherence.
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CF气道上皮细胞对PAO1依从性的夸张的细胞因子反应的关系。

DOI:
10.1186/1465-9921-6-69
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发表时间:
2005-07-11
影响因子:
5.8
通讯作者:
Davis, PB
Davis, PB
中科院分区:
医学2区
文献类型:
--
作者:
Kube, DM;Fletcher, D;Davis, PB

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在许多模型系统中,培养物中的囊性纤维化(CF)表型气道上皮细胞以比匹配对照更大的白细胞介素(IL)-8和IL-6分泌响应铜绿假单胞菌。为了测试这种过度的炎症反应是否是由于报告的铜绿假单胞菌对CF细胞粘附增加而导致的,我们比较了配对的CF和非CF气道上皮细胞系与GFP-PAO 1(一种标记有GFP-PAO 1的假单胞菌菌株)的结合的炎症反应。绿色荧光蛋白。GFP-PAO 1结合和响应PAO 1的细胞因子产生之间没有明确的关系。与CF表型细胞相比,用外源性aGM 1处理导致更大的GFP-PAO 1与正常表型的结合,但是CF细胞系的细胞因子产生仍然更大。当用神经氨酸酶处理细胞时,CF和nonCF表型细胞系之间的PAO 1粘附是均衡的,但是CF表型细胞中响应于炎症刺激的IL-8产生仍然更大。极化细胞系16 HBEo-正义(正常表型)和反义(CF表型)细胞用于测试破坏紧密连接的效果,这允许PAO 1进入两种细胞系中的基底外侧结合位点。CF细胞IL-8的产生增加,而正常细胞则没有。这些数据表明,细菌与CF表型细胞结合的增加本身不能解释CF气道上皮细胞中过量的细胞因子产生,鼓励对替代假设的研究,并提示对CF提出的治疗策略(包括在假单胞菌感染面前破坏紧密连接)的谨慎。
In many model systems, cystic fibrosis (CF) phenotype airway epithelial cells in culture respond to P. aeruginosa with greater interleukin (IL)-8 and IL-6 secretion than matched controls. In order to test whether this excess inflammatory response results from the reported increased adherence of P. aeruginosa to the CF cells, we compared the inflammatory response of matched pairs of CF and non CF airway epithelial cell lines to the binding of GFP-PAO1, a strain of pseudomonas labeled with green fluorescent protein. There was no clear relation between GFP-PAO1 binding and cytokine production in response to PAO1. Treatment with exogenous aGM1 resulted in greater GFP-PAO1 binding to the normal phenotype compared to CF phenotype cells, but cytokine production remained greater from the CF cell lines. When cells were treated with neuraminidase, PAO1 adherence was equalized between CF and nonCF phenotype cell lines, but IL-8 production in response to inflammatory stimuli was still greater in CF phenotype cells. The polarized cell lines 16HBEo-Sense (normal phenotype) and Antisense (CF phenotype) cells were used to test the effect of disrupting tight junctions, which allows access of PAO1 to basolateral binding sites in both cell lines. IL-8 production increased from CF, but not normal, cells. These data indicate that increased bacterial binding to CF phenotype cells cannot by itself account for excess cytokine production in CF airway epithelial cells, encourage investigation of alternative hypotheses, and signal caution for therapeutic strategies proposed for CF that include disruption of tight junctions in the face of pseudomonas infection.
DOI: 10.1164/rccm.200207-765oc
发表时间: 2004-03-01
影响因子: 24.7
作者:
Becker, MN;Sauer, MS;Randell, SH
通讯作者: Randell, SH
DOI: 10.1183/09031936.03.00031803
发表时间: 2003-04-01
影响因子: 24.3
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影响因子: 6.4
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DOI: 10.1183/09031936.01.17100270
发表时间: 2001-01-01
影响因子: 24.3
作者:
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通讯作者: Alton, EWFW