Src kinase Lyn is crucial for Pseudomonas aeruginosa internalization into lung cells
Src kinase Lyn is crucial for Pseudomonas aeruginosa internalization into lung cells
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DOI：
10.1002/eji.200635973
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发表时间：
2006-07-01
影响因子：
5.4
通讯作者：
Wu, Min
中科院分区：
文献类型：
--
作者：
Kannan, Shibichakravarthy;Audet, Aaron;Wu, Min
林恩是Src酪氨酸激酶家族的一种重要的B细胞信号传导激酶，具有从细胞骨架变化到诱导细胞凋亡的广泛功能。然而，林恩在传染病中的作用尚不清楚。在这里，我们证明，林恩激活磷酸化显着影响入侵的肺泡上皮细胞系，原代肺细胞，和大鼠肺的铜绿假单胞菌（PA），一种常见的机会性肺部病原体影响个人与肺免疫缺陷。我们的研究结果表明，林恩的激活及其与筏和TLR 2的相互作用，发挥了重要的作用，在PA与宿主细胞相互作用的初始阶段。使用药理学Src特异性抑制剂PP 2（一种显性阴性突变体）进一步评价了林恩的作用，并最终用Lyn-deficient（林恩（-/-））骨髓源性肥大细胞证实。通过上述方法抑制林恩的功能阻止PA内化。此外，阻断林恩还影响下游事件：诱导炎性细胞因子和细胞凋亡。本报告提出了林恩在传染病中的新作用，并指出了预防和治疗感染的潜在新靶点。
Lyn is an important B cell signaling kinase of the Src tyrosine kinase family with a broad range of functions from cytoskeletal changes to induction of apoptosis. However, the role of Lyn in infectious diseases is not clear. Here, we demonstrate that Lyn activation by phosphorylation significantly impacted invasion of an alveolar epithelial cell line, primary lung cells, and rat lungs by Pseudomonas aeruginosa (PA), a common opportunistic lung pathogen affecting individuals with deficient lung immunity. Our results indicate that activation of Lyn and its interaction with rafts and TLR2, played an important role in the initial stages of PA interaction with host cells. The role of Lyn was further evaluated using the pharmacologic Src-specific inhibitor PP2, a dominant negative mutant, and finally confirmed with Lyn-deficient (Lyn(-/-)) bone marrow-derived mast cells. Inhibition of Lyn's function by above approaches prevented PA internalization. Moreover, blocking of Lyn also affected downstream events: induction of inflammatory cytokines and apoptosis. This report brings out a new role of Lyn in infectious diseases and indicates potential new targets for prevention and treatment of infections.