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p300 的下调通过调节 RhoA/ROCK/NF-κB 通路减轻 LPS 诱导的 A549 细胞炎症损伤。

Downregulation of p300 alleviates LPS-induced inflammatory injuries through regulation of RhoA/ROCK/NF-κB pathways in A549 cells.

机构信息

Department of Neonatology, Linyi People's Hospital, Linyi, 276003, China.

Department of Neurology, Linyi People's Hospital, Linyi, 276003, China.

出版信息

Biomed Pharmacother. 2018 Jan;97:369-374. doi: 10.1016/j.biopha.2017.10.104. Epub 2017 Nov 6.

DOI:10.1016/j.biopha.2017.10.104
PMID:29091886
Abstract

Infantile pneumonia is a common disease in children, which affects cardiopulmonary function and even threats to life. Therefore, overall analysis about the mechanism of pathogenesis may be provided a new slight for the treatment of infantile pneumonia. This study aimed to investigate the role of p300 in lipopolysaccharide (LPS)-induced inflammatory injuries in A549 cells. MTT, flow cytometry, qRT-PCR and western blot assays were used to assess the effect of p300 on A549 cells viability, apoptosis and inflammatory cytokines expressions. Furthermore, RhoA/ROCK/NF-κB signaling pathways were analyzed by qRT-PCR and western blot. Results showed that p300 was significantly up-regulated in LPS-treated A549 cells. Knockdown of p300 promoted cell viability, inhibited apoptosis and decreased the expression levels of IL-1β, IL-6 and TNF-α in LPS-treated A549 cells. In addition, knockdown of p300 abolished the activation of the downstream RhoA/ROCK/NF-κB signaling pathways induced by LPS exposure via regulation of RhoA. In conclusion, p300 might be involved in progression of cell inflammatory response and could serve as a novel therapeutic target for clinical treatment of infantile pneumonia.

摘要

婴儿肺炎是儿童的常见病,影响心肺功能,甚至危及生命。因此,对发病机制的全面分析可能为小儿肺炎的治疗提供新的思路。本研究旨在探讨 p300 在脂多糖(LPS)诱导的 A549 细胞炎症损伤中的作用。MTT、流式细胞术、qRT-PCR 和 Western blot 检测用于评估 p300 对 A549 细胞活力、凋亡和炎症细胞因子表达的影响。此外,通过 qRT-PCR 和 Western blot 分析 RhoA/ROCK/NF-κB 信号通路。结果表明,LPS 处理的 A549 细胞中 p300 明显上调。p300 敲低促进细胞活力,抑制凋亡,并降低 LPS 处理的 A549 细胞中 IL-1β、IL-6 和 TNF-α 的表达水平。此外,p300 敲低通过调节 RhoA 消除了 LPS 暴露诱导的下游 RhoA/ROCK/NF-κB 信号通路的激活。总之,p300 可能参与细胞炎症反应的进展,可作为小儿肺炎临床治疗的新靶点。

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