Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Republic of Korea.
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, Nankai University, Tianjin 300071, China.
Comp Immunol Microbiol Infect Dis. 2019 Dec;67:101373. doi: 10.1016/j.cimid.2019.101373. Epub 2019 Oct 21.
IL-1β expression is increased in response to P. aeruginosa infection, but the responsible proteins have not been clearly elucidated. Here, we demonstrate for the first time that IL-1β expression is induced in response to the heat shock protein 70-like protein DnaK. Treatment with recombinant DnaK (rDnaK) increased IL-1β expression in a dose- and time-dependent manner, and the release of mature IL-1β in response to rDnaK was detected to an extent similar to that stimulated by the well-known agonists, lipopolysaccharide and nigericin. rDnaK-mediated IL-1β expression was driven by the NF-κB signaling pathway. In addition, expression was controlled by the JNK signaling pathway, although these two signaling cascades act independently upon rDnaK stimulation. Finally, rDnaK-induced IL-1β expression was initiated via the action of TLR4. Taken together, the data reveal that P. aeruginosa-derived DnaK induces expression of IL-1β via TLR4-dependent activation of the NF-κB and JNK signaling pathways.
IL-1β 的表达在应对绿脓假单胞菌感染时会增加，但负责的蛋白质尚未明确阐明。在这里，我们首次证明，IL-1β 的表达是由热休克蛋白 70 样蛋白 DnaK 诱导的。重组 DnaK（rDnaK）的处理以剂量和时间依赖的方式增加了 IL-1β 的表达，并且检测到 rDnaK 刺激的成熟 IL-1β 的释放程度与众所周知的激动剂脂多糖和 Nigericin 刺激的释放程度相似。rDnaK 介导的 IL-1β 表达是由 NF-κB 信号通路驱动的。此外，表达受到 JNK 信号通路的控制，尽管这两个信号级联在 rDnaK 刺激下独立作用。最后，rDnaK 诱导的 IL-1β 表达是通过 TLR4 的作用启动的。总之，这些数据表明，绿脓假单胞菌衍生的 DnaK 通过 TLR4 依赖性激活 NF-κB 和 JNK 信号通路诱导 IL-1β 的表达。
