The role of TLR3/NF-kappa B signaling pathway in paraquat-induced acute lung injury

作者：蒋云飞, Yunfei Jiang, 孙昊, Hao Sun, 张劲松, Jinsong Zhang, 吕梦倩, Lv Mengqian, Feng Zhang, Feng Zhang, 宋扬, Song‐I Yang, 臧松松, Songsong Zang, Jun Wang, Jun Wang · 发表于：Zhonghua jizhen yixue zazhi · 年份：2018 · DOI：10.3760/cma.j.issn.1671-0282.2018.06.013 · 研究领域：Paraquat toxicity studies and treatments

Objective To investigate the pathogenesis of paraquat (PQ) induced acute lung injury through Toll like receptor 3 (Toll-like receptor-3, TLR3), TLR induced nuclear transcription factors (Nuclear Factor- kappa B, NF-κB) and its downstream pro-inflammatory factors TNF-α, IL-1β, IL-6. Methods The acute lung injury model of mice and the acute injury model of type II alveolar epithelial cells (A549) induced by PQ were established. The PQ mediated pathological changes of lung tissue, the cell count and cytospin of bronchoalveolar lavage fluid (BALF) were evaluated, and the pro-inflammatory factors in the lung tissue of mice were determined by ELISA the viability of A549 cells mediated by PQ was detected by CCK8 assay, and the mRNA expression and protein level of TLR3, Phospho-NF-kBp65, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in the lung tissues and A549 cells were observed by Real-time PCR and Western-blotting. In control group, the mice received normal saline (NS) instead of PQ. Results Compared with the control group, the mice in PQ group showed difficulty breathing, decreased activity, reduced food intake, and weight lost. The total number of BALF cells in the PQ group was significantly increased [NS: (0.018 8±0.102 1)×105vs. PQ: (0.237 4 ± 0.121 7)×105, t=9.804, P<0.01] with macrophage [NS: (0.162 8±0.086 5)×105vs. PQ: (1.063 3 ± 0.343 3)×105, t=8.043, P<0.01], lymphocyte [NS: (0.006 6±0.005 2)×105vs. PQ: (0.171 2 ± ...