Lyn regulates inflammatory responses in Klebsiella pneumoniae infection via the p38/NF-κB pathway.
Lyn regulates inflammatory responses in Klebsiella pneumoniae infection via the p38/NF-κB pathway.
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Lyn通过p38/NF-κB信号通路调控肺炎克雷伯菌感染中的炎症反应。
DOI：
10.1002/eji.201343972
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发表时间：
2014-03
影响因子：
5.4
通讯作者：
Wu, Min
中科院分区：
文献类型：
--
作者：
Li, Xuefeng;Zhou, Xikun;Ye, Yan;Li, Yi;Li, Jiaxin;Privratsky, Breanna;Wu, Erxi;Gao, Hongwei;Huang, Canhua;Wu, Min
肺炎克雷伯菌是院内感染最常见的病原菌之一，对多种药物的耐药性日益增强。然而，这种细菌的潜在分子发病机制仍然难以捉摸，限制了治疗选择。了解其发病机制有助于抗菌治疗药物的发展。在这里，我们展示了Lyn，一种多效性的Src酪氨酸激酶，通过调节吞噬过程和同时下调炎症反应而参与宿主对肺炎克雷伯菌的防御。采用小鼠急性感染模型，我们观察到LYN−/−小鼠比野生型小鼠更容易感染KP，死亡率增加，肺损伤严重。Kp感染-LYN−/−小鼠表现出炎症细胞因子(IL-6和肿瘤坏死因子-α)升高，肺和其他器官中超氧化物歧化。此外，Kp感染LYNκ小鼠后，p38和NF-−/−B p65亚基的磷酸化水平显著升高。我们还证实了Lyn siRNA敲除后，培养的小鼠肺上皮细胞中p65从胞浆到胞核的转位增加。此外，脂筏与活化的LYN聚集，并聚集在KP侵袭部位。综上所述，这些发现表明LYN可能通过炎症细胞因子的负性调节参与宿主对KP感染的防御。
Klebsiella pneumoniae is one of the most common pathogens in nosocomial infections and is becoming increasingly multidrug-resistant. However, the underlying molecular pathogenesis of this bacterium remains elusive, limiting the therapeutic options. Understanding the mechanism of its pathogenesis may facilitate the development of antibacterial therapeutics. Here, we show that Lyn, a pleiotropic Src tyrosine kinase, is involved in host defense against K. pneumoniae (Kp) by regulating phagocytosis process and simultaneously downregulating inflammatory responses. Using acute infection mouse models, we observed that lyn−/− mice were more susceptible to Kp with increased mortality and severe lung injury compared with wild-type mice. Kp infected-lyn−/− mice exhibited elevated inflammatory cytokines (IL-6 and TNF-α), and increased superoxide in the lung and other organs. In addition, the phosphorylation of p38 and NF-κB p65 subunit increased markedly in response to Kp infection in lyn−/− mice. We also demonstrated that the translocation of p65 from cytoplasm to nuclei increased in cultured murine lung epithelial cells by Lyn siRNA knockdown. Furthermore, lipid rafts clustered with activated Lyn and accumulated in the site of Kp invasion. Taken together, these findings revealed that Lyn may participate in host defense against Kp infection through the negative modulation of inflammatory cytokines.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
32.4
作者：
Cornall, RJ;Cyster, JG;Goodnow, CC
通讯作者：
Goodnow, CC
DOI：
10.1165/ajrcmb.25.6.4550
发表时间：
2001-12-01
影响因子：
6.4
作者：
He, YH;Wu, M;Martin, WJ
通讯作者：
Martin, WJ
影响因子：
6.7
作者：
Dai S;Rajaram MV;Curry HM;Leander R;Schlesinger LS
通讯作者：
Schlesinger LS
影响因子：
3.7
作者：
Kannan S;Huang H;Seeger D;Audet A;Chen Y;Huang C;Gao H;Li S;Wu M
通讯作者：
Wu M