Pathogenic bacteria induce colonic PepT1 expression: an implication in host defense response.
Pathogenic bacteria induce colonic PepT1 expression: an implication in host defense response.
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DOI：
10.1053/j.gastro.2009.06.043
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发表时间：
2009-10
期刊：
影响因子：
29.4
通讯作者：
Merlin D
中科院分区：
文献类型：
--
作者：
Nguyen HT;Dalmasso G;Powell KR;Yan Y;Bhatt S;Kalman D;Sitaraman SV;Merlin D
已经在炎症条件下的结肠中观察到二/三肽转运蛋白PepT 1的表达，然而，诱导因素和潜在机制仍然未知。在这里，我们解决了致病菌对结肠PepT 1表达的影响及其功能后果。人结肠HT 29-C1.19A细胞用附着和消失（A/E）肠致病性E. coli（EPEC）。野生型和PepT 1转基因小鼠或来自这些小鼠的培养的结肠组织感染啮齿柠檬酸杆菌，一种与EPEC相关的鼠A/E病原体。EPEC通过脂筏与宿主细胞紧密结合，诱导HT 29-Cl.19A细胞中PepT 1的表达和活性。EPEC对PepT 1表达的诱导需要转录因子Cdx 2。PepT 1的表达降低了EPEC与脂筏的结合，以及NF-κB和MAP激酶的激活和IL-8的产生。因此，离体和体内实验表明，C。啮齿目线虫感染的转基因小鼠诱导结肠PepT 1表达，与野生型小鼠相比，感染啮齿目线虫的PepT 1转基因小鼠的结肠PepT 1表达显著增加。啮齿动物表现出减少的细菌定植、促炎细胞因子的产生和中性粒细胞浸润到结肠中。我们的研究结果表明，结肠PepT 1的表达在病理条件下的调节的分子机制，并揭示了PepT 1在宿主防御通过其调节细菌-上皮相互作用和肠道炎症的能力的新作用。
Expression of the di/tripeptide transporter PepT1 has been observed in the colon under inflammatory conditions, however, the inducing factors and underlying mechanisms remain unknown. Here, we address the effects of pathogenic bacteria on colonic PepT1 expression together with its functional consequences. Human colonic HT29-Cl.19A cells were infected with the attaching and effacing (A/E) enteropathogenic E. coli (EPEC). Wild-type and PepT1 transgenic mice or cultured colonic tissues derived from these mice were infected with Citrobacter rodentium, a murine A/E pathogen related to EPEC. EPEC induced PepT1 expression and activity in HT29-Cl.19A cells by intimately attaching to host cells through lipid rafts. Induction of PepT1 expression by EPEC required the transcription factor Cdx2. PepT1 expression reduced binding of EPEC to lipid rafts, as well as activation of NF-κB and MAP kinase and production of IL-8. Accordingly, ex vivo and in vivo experiments revealed that C. rodentium induced colonic PepT1 expression and that, compared to their wild-type counterparts, PepT1 transgenic mice infected with C. rodentium exhibited decreased bacterial colonization, production of pro-inflammatory cytokines, and neutrophil infiltration into the colon. Our findings demonstrate a molecular mechanism underlying the regulation of colonic PepT1 expression under pathological conditions and reveal a novel role for PepT1 in host defense via its capacity to modulate bacterial-epithelial interactions and intestinal inflammation.
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影响因子：
3.7
作者：
Dalmasso G;Nguyen HT;Yan Y;Charrier-Hisamuddin L;Sitaraman SV;Merlin D
通讯作者：
Merlin D
影响因子：
3.1
作者：
Hicks, S;Frankel, G;Phillips, AD
通讯作者：
Phillips, AD
影响因子：
3.1
作者：
Borenshtein, Diana;Nambiar, Prashant R.;Schauer, David B.
通讯作者：
Schauer, David B.
影响因子：
3.4
作者：
Allen-Vercoe, E;Waddell, B;DeVinney, R
通讯作者：
DeVinney, R
影响因子：
5.8
作者：
Shimakura, Jin;Terada, Tomohiro;Inui, Ken-ichi
通讯作者：
Inui, Ken-ichi