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      저자 : Huixin Tang (검색결과 1 건)
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        Mst1/2-ALK promotes NLRP3 inflammasome activation and cell apoptosis during Listeria monocytogenes infection

        Aijiao Gao,Huixin Tang,Qian Zhang,Ruiqing Liu,Lin Wang,Yashan Liu,Zhi Qi,Yanna Shen 한국미생물학회 2021 The journal of microbiology Vol.59 No.7

        Listeria monocytogenes (L. monocytogenes) is a Gram-positiveintracellular foodborne pathogen that causes severe diseases,such as meningitis and sepsis. The NLR family pyrindomain-containing 3 (NLRP3) inflammasome has been reportedto participate in host defense against pathogen infection. However, the exact molecular mechanisms underlyingNLRP3 inflammasome activation remain to be fully elucidated. In the present study, the roles of mammalian Ste20-like kinases 1/2 (Mst1/2) and Anaplastic Lymphoma Kinase(ALK) in the activation of the NLRP3 inflammasome inducedby L. monocytogenes infection were investigated. Theexpression levels of Mst1/2, phospho (p)-ALK, p-JNK, Nek7,and NLRP3 downstream molecules including activated caspase-1 (p20) and mature interleukin (IL)-1β (p17), were upregulatedin L. monocytogenes-infected macrophages. TheALK inhibitor significantly decreased the expression of p-JNK,Nek7, and NLRP3 downstream molecules in macrophages infectedwith L. monocytogenes. Furthermore, the Mst1/2 inhibitormarkedly inhibited the L. monocytogenes-induced activationof ALK, subsequently downregulating the expressionof p-JNK, Nek7, and NLRP3 downstream molecules. Therefore,our study demonstrated that Mst1/2-ALK mediatedthe activation of the NLRP3 inflammasome by promotingthe interaction between Nek7 and NLRP3 via JNK duringL. monocytogenes infection, which subsequently increased thematuration and release of proinflammatory cytokine to resistpathogen infection. Moreover, Listeriolysin O played akey role in the process. In addition, we also found that the L. monocytogenes-induced apoptosis of J774A.1 cells was reducedby the Mst1/2 or ALK inhibitor. The present study reported,for the first time, that the Mst1/2-ALK-JNK-NLRP3 signalingpathway plays a vital proinflammatory role during L. monocytogenesinfection.

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