细胞内膜网膜应激增强了TLR3诱导的TSLP通过气道表皮表达
Prabuddha S Pathinayake1, Alan C-Y Hsu1,2, Kristy S Nichol1
1Immune Health Program, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
概括
细胞内膜网膜 (ER) 应激会通过PERK-CHOP通路诱导胸膜 stromal lymphopoietin (TSLP) mRNA,并增强TSLP蛋白质分泌. 这种TSLP的ER压力启动可能会导致严重的喘恶化.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 呼吸系统医学 呼吸系统医学
背景情况:
- 胸膜 stromal 淋巴蛋白 (TSLP) 是重症喘发病的一个关键细胞因子.
- 细胞内膜网膜 (ER) 的压力与喘的发展有关.
- 在气道上皮质中TSLP诱导中ER应激的作用尚不清楚.
研究的目的:
- 调查ER应激和未折叠蛋白反应 (UPR) 信号是否会在气道上皮质中诱导TSLP.
- 为了确定参与ER压力诱导TSLP的信号通路.
- 在喘患者中关联ER压力和TSLP表达.
主要方法:
- 用ER压力诱导剂治疗人类支气管上皮细胞.
- 对TSLP mRNA和蛋白质表达的测量.
- siRNA基因敲除以确定信号通路.
- 来自喘患者的支气管活检cDNA的分析.
主要成果:
- 通过PERK-C/EBP同源蛋白 (CHOP) 途径,ER应激信号诱导TSLP mRNA.
- AP-1转录因子对于ER压力诱导的TSLP mRNA至关重要.
- ER压力增强了TLR3诱导的TSLP蛋白质分泌.
- TSLP和ER压力 (PERK) mRNA在喘中具有正相关性,特别是中性友性喘.
结论:
- ER压力原始化TSLP,该TSLP通过TLR3激活进一步增强,可能导致严重的喘恶化.
- 针对ER压力可能为严重不受控制的喘提供新的治疗策略.
- 确定了一种将ER压力与空气道上皮质TSLP上调相关的新机制.
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