S100A8/A9 is not involved in host defense against murine urinary tract infection.
S100A8/A9 is not involved in host defense against murine urinary tract infection.
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DOI：
10.1371/journal.pone.0013394
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发表时间：
2010-10-14
期刊：
影响因子：
3.7
通讯作者：
Leemans JC
中科院分区：
文献类型：
--
作者：
Dessing MC;Butter LM;Teske GJ;Claessen N;van der Loos CM;Vogl T;Roth J;van der Poll T;Florquin S;Leemans JC
炎症通常伴随着内源性蛋白质的释放，称为危险相关分子模式（DAMP），能够警告宿主显著的危险。S100 A8/A9亚基是属于钙结合蛋白S100家族的DAMP。S100 A8/A9复合物诱导炎性反应，并且它们的表达与几种炎性病症中的疾病严重程度相关。S100 A8/A9促进内毒素和大肠杆菌（Escherichia（E.）大肠杆菌诱导的脓毒症显示其在全身感染中的作用。S100 A8/A9在大肠埃希菌引起的泌尿系统局部感染中的作用大肠杆菌仍然未知。我们通过滴注2种不同剂量的尿路致病性大肠杆菌，研究S100 A8/A9在急性尿路感染（UTI）中的作用。大肠杆菌在野生型（WT）和S100 A9敲除（KO）小鼠中经尿道感染。随后，我们在24小时和48小时后测定膀胱和肾脏中的细菌生长、嗜中性粒细胞浸润和炎症介质。UTI导致WT小鼠膀胱和肾组织中S100 A8/A9蛋白的显著增加。在2个不同时间点使用2种不同剂量时，S100 A9 KO小鼠的膀胱或肾匀浆中的细菌负荷与WT小鼠相似。S100 A9缺陷对E.大肠杆菌诱导的UTI感染，通过膀胱和肾脏中的髓过氧化物酶活性、组织病理学分析以及肾脏和膀胱细胞因子浓度进行评估。我们发现，尽管在UTI时膀胱和肾组织中S100 A8/A9的高表达，但S100 A8/A9并不有助于有效的宿主对E.泌尿系统中的大肠杆菌。
Inflammation is commonly followed by the release of endogenous proteins called danger associated molecular patterns (DAMPs) that are able to warn the host for eminent danger. S100A8/A9 subunits are DAMPs that belong to the S100 family of calcium binding proteins. S100A8/A9 complexes induce an inflammatory response and their expression correlates with disease severity in several inflammatory disorders. S100A8/A9 promote endotoxin- and Escherichia (E.) coli-induced sepsis showing its contribution in systemic infection. The role of S100A8/A9 during a local infection of the urinary tract system caused by E. coli remains unknown. We investigated the contribution of S100A8/A9 in acute urinary tract infection (UTI) by instilling 2 different doses of uropathogenic E. coli transurethrally in wild type (WT) and S100A9 knockout (KO) mice. Subsequently, we determined bacterial outgrowth, neutrophilic infiltrate and inflammatory mediators in bladder and kidney 24 and 48 hours later. UTI resulted in a substantial increase of S100A8/A9 protein in bladder and kidney tissue of WT mice. S100A9 KO mice displayed similar bacterial load in bladder or kidney homogenate compared to WT mice using 2 different doses at 2 different time points. S100A9 deficiency had little effect on the inflammatory responses to E. Coli-induced UTI infection, as assessed by myeloperoxidase activity in bladder and kidneys, histopathologic analysis, and renal and bladder cytokine concentrations. We show that despite high S100A8/A9 expression in bladder and kidney tissue upon UTI, S100A8/A9 does not contribute to an effective host response against E. Coli in the urinary tract system.
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影响因子：
16.8
作者：
Roth, J;Vogl, T;Sunderkötter, C
通讯作者：
Sunderkötter, C
影响因子：
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