title: Lyn regulates inflammatory responses in Klebsiella pneumoniae infection via the p38/NF-κB pathway.
abstract: Klebsiella pneumoniae (Kp) 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 anti-bacterial therapeutics. Here, we show that Lyn, a pleiotropic Src tyrosine kinase, is involved in host defense against 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 WT 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.
authors: The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P. R. China; Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, ND, USA.
authors: Xuefeng
authors: X
authors: Li
authors: Xikun
authors: X
authors: Zhou
authors: Yan
authors: Y
authors: Ye
authors: Yi
authors: Y
authors: Li
authors: Jiaxin
authors: J
authors: Li
authors: Breanna
authors: B
authors: Privratsky
authors: Erxi
authors: E
authors: Wu
authors: Hongwei
authors: H
authors: Gao
authors: Canhua
authors: C
authors: Huang
authors: Min
authors: M
authors: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D007710:Klebsiella Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D007711:Klebsiella pneumoniae; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000401:mortality; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Bacterial pathogenesis; Bioluminescence; Cytokinesis; Infectious diseases; Klebsiella pneumoniae; Lyn