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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2024, Vol. 17 ›› Issue (02) : 207 -211. doi: 10.3877/cma.j.issn.1674-6902.2024.02.007

论著

PM2.5通过激活颗粒酶B/IL-18信号通路促进炎症因子表达
陈向军1, 王在强2, 王博荣1, 王莉1, 方芳1, 金发光2, 王光辉1,†()   
  1. 1. 710100　西安，西安市胸科医院重症医学二科
    2. 710038　西安，空军军医大学第二附属医院呼吸与危重症医学科
  • 收稿日期:2023-08-25 出版日期:2024-04-25
  • 通信作者: 王光辉
  • 基金资助:
    陕西省重点研发计划(2018ZDCXL-SF-02-03-02)

PM2.5 promoted the expression of inflammatory cytokines by activating granzyme B/IL-18 signaling pathway

Xiangjun Chen1, Zaiqiang Wang2, Borong Wang1, Li Wang1, Fang Fang1, Faguang Jin2, Guanghui Wang1,†()   

  1. 1. The second Department of Intensive Care Medicine, Xi′an Chest Hospital, Xi′an 710100, China
    2. Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Air Force Medical University, Xi′an 710038, China
  • Received:2023-08-25 Published:2024-04-25
  • Corresponding author: Guanghui Wang
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陈向军, 王在强, 王博荣, 王莉, 方芳, 金发光, 王光辉. PM2.5通过激活颗粒酶B/IL-18信号通路促进炎症因子表达[J]. 中华肺部疾病杂志(电子版), 2024, 17(02): 207-211.

Xiangjun Chen, Zaiqiang Wang, Borong Wang, Li Wang, Fang Fang, Faguang Jin, Guanghui Wang. PM2.5 promoted the expression of inflammatory cytokines by activating granzyme B/IL-18 signaling pathway[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2024, 17(02): 207-211.

目的

分析颗粒酶B在PM2.5促进自然杀伤(natural killer, NK)细胞炎症因子表达中的作用。

方法

(1)通过设置PM2.5染毒剂量梯度，分组为空白对照组(0 μg/ml)、PM2.5(50 μg/ml)组、PM2.5(150 μg/ml)组和PM2.5(450 μg/ml)组，观察PM2.5暴露与NK细胞颗粒酶B和炎症因子TNF-α、IL-1β表达间有无相关性；(2)为明确PM2.5上调NK细胞炎症因子表达中颗粒酶B是否发挥促进作用，根据是否行PM2.5染毒和颗粒酶B抑制剂Serpina3n预处理，实验分为空白对照组、Serpina3n组、PM2.5组和Serpina3n＋PM2.5组。在PM2.5染毒前1h，Serpina3n组和Serpina3n＋PM2.5组加入Serpina3n(100 ng/ml)；(3)为明确在PM2.5上调NK细胞炎症因子表达中颗粒酶B是否通过IL-18发挥作用，根据是否行PM2.5染毒和IL-18抑制剂IL-18BP预处理，实验分为空白对照组、IL-18BP、PM2.5组、IL-18BP＋PM2.5组。在PM2.5染毒前1 h，IL-18BP组和IL-18BP＋PM2.5组加入IL-18BP (100 ng/ml)。分别检测每组NK细胞蛋白表达情况和细胞培养液TNF-α、IL-1β水平。

结果

PM2.5促进了NK细胞颗粒酶B和炎症因子TNF-α、IL-1β表达；阻断颗粒酶B抑制NK细胞IL-18表达和NF-κB磷酸化，降低TNF-α和IL-1β表达；阻断IL-18抑制了NF-κB磷酸化，降低TNF-α和IL-1β表达。

结论

PM2.5可能通过激活颗粒酶B/IL-18信号通路促进NK细胞TNF-α和IL-1β表达，机制可能与激活NF-κB信号通路有关。

关键词: PM2.5, 颗粒酶B, 自然杀伤细胞, 炎症因子
Objective

To explore the role of granzyme B in PM2.5 promoting the expression of inflammatory cytokines in natural killer (NK) cells.

Methods

First, the PM2.5 dose gradient was set. The experiment was divided into blank control group (0 μg/ml), PM2.5 group (50 μg/ml), PM2.5 group (150 μg/ml), and PM2.5 group (450 μg/ml). By setting the PM2.5 dose gradient, we observed the correlation between the expression of NK cell granzyme B and inflammatory cytokines TNF-α and IL-1β. Second, in order to determine whether granzyme B plays a promoting role in the expression of inflammatory cytokines in NK cells promoted by PM2.5, the experiment was divided into blank control group, Serpina3n group, PM2.5 group and Serpina3n+ PM2.5 group according to whether PM2.5 exposure and Serpina3n inhibitor were pretreated. Serpina3n group and Serpina3n+ PM2.5 group were added Serpina3n(100 ng/ml) 1 hour before PM2.5 poisoning. Third, in order to determine whether granzyme B plays a role through IL-18 in PM2.5 promoting the expression of inflammatory cytokines in NK cells, the experiment was divided into blank control group, IL-18BP, PM2.5 group, and IL-18BP+ PM2.5 group according to whether PM2.5 exposure and IL-18BP inhibitor were pretreated. One hour before PM2.5 exposure, IL-18BP group and IL-18BP+ PM2.5 group were added with IL-18BP (100 ng/ml). The expression of NK cell protein and the levels of TNF-α and IL-1β in cell culture medium were detected in each group separately.

Results

PM2.5 promoted the expression of granzyme B and inflammatory factors TNF-α and IL-1β in NK cells. Blocking granzyme B inhibited IL-18 expression and NF-κB phosphorylation, and decreased TNF-α and IL-1β expression in NK cells. Blocking IL-18 inhibited the phosphorylation of NF-κB and decreased the expression of TNF-α and IL-1β.

Conclusion

PM2.5 may promote the expression of TNF-α and IL-1β in NK cells by activating granzyme B/IL-18 signaling pathway, and the mechanism may be related to the activation of NF-κB signaling pathway.

Key words: Particulate Matter 2.5, Granzyme B, Natural killer cell, Inflammatory cytokine
图1 不同处理组细胞颗粒酶B表达情况。注：***P<0.001
图2 不同处理组细胞培养液TNF-α和IL-1β水平。注：**P<0.01，***P<0.001
图3 不同处理组细胞颗粒酶B、IL-18表达和NF-κB磷酸化情况。注：p-NF-κB: phosphorylated NF-κB，*P<0.05，***P<0.001，n.s.表示无统计学差异
图4 不同处理组细胞培养液TNF-α和IL-1β水平；注：***P<0.001，n.s.表示无统计学差
图5 不同处理组细胞颗粒酶B、IL-18表达和NF-κB磷酸化情况。注：p-NF-κB：phosphorylated NF-κB，*P<0.05，***P<0.001，n.s.表示无统计学差异
图6 不同处理组细胞培养液TNF-α和IL-1β水平。注：***P<0.001，n.s.表示无统计学差异
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