在呼吸道感染期间,Ki-67促进炎症信号,控制中性粒细胞的招募
Min Yee1, Ravi Misra1, Sarah Vesecky1
1Division of Neonatology, Department of Pediatrics, School of Medicine & Dentistry, The University of Rochester, Rochester, NY, USA.
EMBO molecular medicine
|June 10, 2025
概括
早期的环境暴露,如高氧化,可以增加肺细胞中的Ki-67表达,导致呼吸道感染期间更大的中性粒细胞招募和急性肺损伤 (ALI).
科学领域:
- 肺部医学 肺部医学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 中性粒细胞对抗呼吸道感染至关重要,但在过度招募时可能导致急性肺损伤 (ALI).
- 早期生活环境因素影响肺部发育,但它们对中性粒细胞招募的影响尚不清楚.
研究的目的:
- 为了研究早期生活环境因素如何影响中性粒细胞招募和成年小鼠的肺炎.
- 确定基-67增殖标记在上皮细胞化学基因产生和中性粒细胞招募中的作用.
主要方法:
- 将新生小鼠暴露在高氧和评估成年肺组织的膜1型 (AT1) 细胞表达Ki-67.
- 用A型流感病毒感染小鼠或将它们暴露在脂多糖化物 (LPS) 中,以评估中性粒细胞的招募和化学激素的产生.
- 使用基67低形状小鼠和基因工程小鼠过度表达基67的基因.
- 利用siRNA在小鼠AT1-样细胞系中使Ki-67沉默,以评估其对化学基因基因表达的影响.
主要成果:
- 新生儿高氧化暴露增加了成年AT1细胞中的Ki-67表达,与增加的化学激素产生相关.
- 这些Ki-67表达AT1细胞在病毒感染或LPS挑战期间促进了中性粒细胞的招募和ALI.
- 调节Ki-67水平 (低形态或过度表达) 改变了中性粒细胞的招募和化学激素的产生.
- 在AT1-样细胞中,Ki-67的沉默降低了NF-κB依赖化学基因 (Cxcl1,Cxcl5) 的基底和IL-1β诱导的表达.
结论:
- 基-67在调节上皮质前炎信号传递方面发挥着新的作用,从而控制中性粒细胞向肺部招募.
- 提高Ki-67表达的环境因素和辅原体可能会影响呼吸道感染的严重程度.
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