Increased inflammation and lethality of Dusp1-/- mice in polymicrobial peritonitis models
Increased inflammation and lethality of Dusp1-/- mice in polymicrobial peritonitis models
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DOI：
10.1111/j.1365-2567.2010.03313.x
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发表时间：
2010-11-01
期刊：
影响因子：
6.4
通讯作者：
Lang, Roland
中科院分区：
文献类型：
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作者：
Hammer, Michael;Echtenachter, Bernd;Lang, Roland
丝裂原活化蛋白激酶磷酸酶Dusp 1（也称为MKP-1）对于控制革兰氏阴性菌脂多糖全身攻击的炎症反应至关重要。在这里，我们研究了Dusp 1缺陷在升结肠支架腹膜炎（CASP）和盲肠结扎穿孔（CLP），两种小鼠模型的脓毒性腹膜炎的后果。CASP后，Dusp 1-/-小鼠的CCL 4、白细胞介素-10（IL-10）和IL-6的血清水平升高，与野生型小鼠的差异取决于脓毒症的严重程度。这些细胞因子，沿着诱导型一氧化氮合酶信使RNA，在脾脏和肝脏中也以较高水平表达。在CLP模型中检测到类似的这些细胞因子的过度产生，与野生型小鼠的差异甚至更大。尽管炎症反应增加，但在接受CASP和CLP的Dusp 1-/-小鼠中细菌清除受损。Dusp 1-/-小鼠在两种腹膜炎模型中的致死率均增加。总之，我们的数据表明，在缺乏Dusp 1的情况下，对引入腹膜的肠道细菌的过度炎症反应无助于控制细菌复制，但对宿主有害。
P>The mitogen-activated protein kinase phosphatase Dusp1 (also known as MKP-1) is essential for control of the inflammatory response to systemic challenge with the lipopolysaccharide of Gram-negative bacteria. Here, we have investigated the consequences of Dusp1-deficiency in colon ascendens stent peritonitis (CASP) and caecal ligation and puncture (CLP), two mouse models of septic peritonitis. Following CASP, Dusp1-/- mice had increased serum levels of CCL4, interleukin-10 (IL-10) and IL-6, with differences from wild-type mice being dependent on severity of sepsis. These cytokines, along with inducible nitric oxide synthase messenger RNA, were also expressed at higher levels in spleen and liver. Similar over-production of these cytokines was detected in the CLP model, with even larger differences from wild-type mice. Despite the increased inflammatory response, bacterial clearance was impaired in Dusp1-/- mice subjected to CASP and CLP. Dusp1-/- mice suffered increased lethality in both peritonitis models. Together our data indicate that exaggerated inflammatory responses to gut bacteria introduced into the peritoneum in the absence of Dusp1 do not help to control bacterial replication but are detrimental for the host.