Dietary flavonoid luteolin attenuates uropathogenic Escherichia. Coli invasion of the urinary bladder
Dietary flavonoid luteolin attenuates uropathogenic Escherichia. Coli invasion of the urinary bladder
复制标题
膳食类黄酮木犀草素可减弱泌尿道致病性大肠杆菌。
DOI：
10.1002/biof.1314
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发表时间：
2016-11-01
期刊：
影响因子：
6
通讯作者：
Huang, Ning
中科院分区：
文献类型：
--
作者：
Shen, Xiao-Fei;Teng, Yan;Huang, Ning
尿路致病性大肠杆菌（UPEC）是主要的尿路病原体，它粘附并侵入膀胱上皮细胞（BEC），从而成功建立尿路感染（UTI）。新出现的抗生素耐药性需要新的非抗生素策略。我们前期的研究表明，毛地黄黄酮通过下调UPEC毒力因子，降低UPEC对T24 BEC的粘附、侵袭能力和细胞毒性。本研究的目的是探讨黄酮类化合物木犀草素的可能功能和机制，木犀草素的功能，在UPEC诱导的膀胱感染。首先，通过菌落计数，观察到木犀草素预处理的5637和T24 BEC以及小鼠膀胱中的UPEC侵袭明显减少，但粘附不明显。木犀草素介导的UPEC侵袭抑制与通过抑制cAMP-磷酸二酯酶（cAMP-PDE）的活性诱导的细胞内cAMP水平升高有关，这导致蛋白激酶A的激活，从而负调节Rac 1-GTP酶介导的肌动蛋白聚合。此外，p38 MAPK和ERK 1/2的化学激活剂证实，p38 MAPK主要和ERK 1/2部分参与木犀草素介导的抑制UPEC侵袭和肌动蛋白聚合。这些数据表明，毛地黄黄酮可以保护膀胱上皮细胞免受UPEC的侵袭。因此，毛地黄黄酮或富含毛地黄黄酮的产品作为膳食补充剂可能有助于控制UPEC相关的膀胱感染，cAMP-PDE可能成为UTIs治疗的靶点。(C)2016年生物因子
Uropathogenic Escherichia coli (UPEC), the primary uropathogen, adhere to and invade bladder epithelial cells (BECs) to establish a successful urinary tract infection (UTI). Emerging antibiotic resistance requires novel nonantibiotic strategies. Our previous study indicated that luteolin attenuated adhesive and invasive abilities as well as cytotoxicity of UPEC on T24 BECs through down-regulating UPEC virulence factors. The aims of this study were to investigate the possible function of the flavonoid luteolin and the mechanisms by which luteolin functions in UPEC-induced bladder infection. Firstly, obvious reduction of UPEC invasion but not adhesion were observed in luteolin-pretreated 5637 and T24 BECs sa well as mice bladder via colony counting. The luteolin-mediated suppression of UPEC invasion was linked to elevated levels of intracellular cAMP induced by inhibiting the activity of cAMP-phosphodiesterases (cAMP-PDEs), which resulting activation of protein kinase A, thereby negatively regulating Rac1-GTPase-mediated actin polymerization. Furthermore, p38 MAPK was primarily and ERK1/2 was partially involved in luteolin-mediated suppression of UPEC invasion and actin polymerization, as confirmed with chemical activators of p38 MAPK and ERK1/2. These data suggest that luteolin can protect bladder epithelial cells against UPEC invasion. Therefore, luteolin or luteolin-rich products as dietary supplement may be beneficial to control the UPEC-related bladder infections, and cAMP-PDEs may be a therapy target for UTIs treatment. (C) 2016 BioFactors