切换至 "中华医学电子期刊资源库"
高级检索
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
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

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
1
王在强，李兰玉，傅恩清，等. PM2.5通过上调颗粒酶B促进IL-18表达加重肺部炎症[J/CD]. 中华肺部疾病杂志(电子版), 2021, 14(6): 734-740.
2
Xing YF, Xu YH, Shi MH, et al. The impact of PM2.5 on the human respiratory system[J]. J Thorac Dis, 2016, 8(1): E69-E74.
3
Feng S, Gao D, Liao F, et al. The health effects of ambient PM2.5 and potential mechanisms[J]. Ecotoxicol Environ Saf, 2016, 128: 67-74.
4
Cho CC, Hsieh WY, Tsai CH, et al. In vitro and in vivo experimental studies of PM2.5 on disease progression[J]. Int J Environ Res Public Health, 2018, 15(7): 1380.
5
Yang B, Guo J, Xiao C. Effect of PM2.5 environmental pollution on rat lung[J]. Environ Sci Pollut Res Int, 2018, 25(36): 36136-36146.
6
袁　玉，彭　璐，陈采陶，等. 肺NK细胞及其在肺部疾病中作用的研究进展[J]. 细胞与分子免疫学杂志，2022, 38(2): 183-190.
7
Cong J, Wei H. Natural killer cells in the lungs[J]. Front Immunol，2019, 10: 1416.
8
Turner CT, Zeglinski MR, Richardson KC, et al. Granzyme B contributes to barrier dysfunction in oxazolone-induced skin inflammation through E-cadherin and FLG cleavage[J]. J Invest Dermatol, 2021, 141(1): 36-47.
9
Bao CX, Chen HX, Mou XJ, et al. GZMB gene silencing confers protection against synovial tissue hyperplasia and articular cartilage tissue injury in rheumatoid arthritis through the MAPK signaling pathway[J]. Biomed Pharmacother, 2018, 103: 346-354.
10
张天宇，Shen Steve, 杨　琳. 颗粒酶B在慢性鼓膜穿孔炎症损伤修复中的应用[J]. 中国眼耳鼻喉科杂志，2016, 16(1): 7-9, 15.
11
Richardson KC, Jung K, Pardo J, et al. Noncytotoxic roles of granzymes in health and disease[J]. Physiology (Bethesda), 2022, 37(6): 323-348.
12
Ma QY, Huang DY, Zhang HJ, et al. Exposure to particulate matter 2.5 (PM2.5) induced macrophage-dependent inflammation, characterized by increased Th1/Th17 cytokine secretion and cytotoxicity[J]. Int Immunopharmacol, 2017, 50: 139-145.
13
Cohen AJ, Brauer M, Burnett R, et al. Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015[J]. Lancet, 2017, 389(10082): 1907-1918.
14
曹丽敏，周　芸，张　庄，等. 环境空气颗粒物及其组分对呼吸系统健康的影响[J]. 中华预防医学杂志，2016, 12: 1114-1118.
15
Li R, Zhou R, Zhang J. Function of PM2.5 in the pathogenesis of lung cancer and chronic airway inflammatory diseases[J]. Oncol Lett, 2018, 15(5): 7506-7514.
16
Wang H, Song L, Ju W, et al. The acute airway inflammation induced by PM2.5 exposure and the treatment of essential oils in Balb/c mice[J]. Sci Rep, 2017, 7: 44256.
17
Zhu RX, Nie XH, Chen YH, et al. Relationship between particulate matter (PM2.5) and hospitalizations and mortality of chronic obstructive pulmonary disease patients: A Meta-analysis[J]. Am J Med Sci, 2020, 359(6): 354-364.
18
Gregoire C, Chasson L, Luci C, et al. The trafficking of natural killer cells[J]. Immunol Rev, 2007, 220(1): 169-182.
19
Qian Q, Chowdhury BP, Sun Z, et al. Maternal diesel particle exposure promotes offspring asthma through NK cell-derived granzyme B[J]. J Clin Invest, 2020，130(8)：4133-4151.
20
Wang L, Jiang S, Xiao L, et al. Inhibition of granzyme B activity blocks inflammation induced by lipopolysaccharide through regulation of endoplasmic reticulum stress signaling in NK92 cells[J]. Mol Med Rep, 2018, 18(1): 580-586.
21
Campos TM, Novais FO, Saldanha M, et al. Granzyme B produced by natural killer cells enhances inflammatory response and contributes to the immunopathology of cutaneous leishmaniasis[J]. J Infect Dis, 2020, 221(6): 973-982.
22
Tremblay GM, Wolbink AM, Cormier Y, et al. Granzyme activity in the inflamed lung is not controlled by endogenous serine proteinase inhibitors[J]. J Immunol, 2000，165(7): 3966-3969.
23
Omoto Y, Yamanaka K, Tokime K, et al. Granzyme B is a novel interleukin-18 converting enzyme[J]. J Dermatol Sci, 2010, 59(2): 129-135.
24
Akeda T, Yamanaka K, Tsuda K, et al. CD8＋ T cell granzyme B activates keratinocyte endogenous IL-18[J]. Arch Dermatol Res, 2014, 306(2): 125-130.
25
Zhou Z, Liu Y, Duan F, et al. Transcriptomic analyses of the biological effects of airborne PM2.5 exposure on human bronchial epithelial cells[J]. PLoS One, 2015, 10(9): e138267.
26
Popadic D, Hesselbach K, Richter-Brockmann S, et al. Gene expression profiling of human bronchial epithelial cells exposed to fine particulate matter (PM2.5) from biomass combustion[J]. Toxicol Appl Pharmacol, 2018, 347: 10-22.
27
Dinarello CA. Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process[J]. Am J Clin Nutr, 2006, 83(2): 447S-455S.
28
Zhang LM, Zhang J, Zhang Y, et al. Interleukin-18 binding protein attenuates lipopolysaccharide-induced acute lung injury in mice via suppression NF-kappaB and activation Nrf2 pathway[J]. Biochem Biophys Res Commun, 2018, 505(3): 837-842.
[1] 孙艺玮, 陈炜, 秦巍, 杜景辰, 孟昕, 周永军. 血管腔内介入治疗糖尿病足合并下肢动脉硬化闭塞症患者术后再狭窄与血清炎症因子的相关性[J]. 中华损伤与修复杂志(电子版), 2024, 19(01): 34-40.
[2] 陈大敏, 曹晓刚, 曹能琦. 肥胖对胃癌患者手术治疗效果的影响研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 651-653.
[3] 杜贵伟, 陆勇, 成博, 贺薏, 梁爽. 钬激光碎石术术后联合坦索罗辛治疗对输尿管结石患者的影响分析[J]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(05): 491-496.
[4] 方慧慧, 方明, 黄娟, 张华, 王晓娟. 布地格福吸入治疗对COPD患者IL-6、CRP水平及肺功能的影响[J]. 中华肺部疾病杂志(电子版), 2024, 17(01): 91-94.
[5] 方晓铵, 熊欢庆, 李玉娟, 刘刚, 金发光. E3泛素连接酶COP-1在脂多糖致小鼠急性肺损伤中的意义[J]. 中华肺部疾病杂志(电子版), 2024, 17(01): 14-18.
[6] 何花, 周玉皆, 李田. 鸦胆子油乳辅助PC方案化疗对NSCLC免疫功能和炎症因子的影响[J]. 中华肺部疾病杂志(电子版), 2023, 16(05): 697-699.
[7] 刘剑, 张燕, 刘春桂, 吉浩明, 鲁小敏. 贝伐珠单抗辅助治疗对晚期非鳞NSCLC患者炎症、免疫和营养指数的影响[J]. 中华肺部疾病杂志(电子版), 2023, 16(05): 694-696.
[8] 刘宝刚, 李磊强, 孙立哲, 耿翠翠. 生物免疫疗法联合放化疗对NSCLC患者CD3＋、CD4＋/CD8＋、NK的影响[J]. 中华肺部疾病杂志(电子版), 2023, 16(05): 661-663.
[9] 陈向军, 顾兴, 王在强, 王光辉, 王莉, 方芳, 金发光, 王瑞璇. 颗粒酶B激活TGF-β1/Smad3通路促进博来霉素导致的肺纤维化[J]. 中华肺部疾病杂志(电子版), 2023, 16(05): 630-634.
[10] 张婵, 吕瑶, 张小燕, 张鸣青. 不同时机局部神经阻滞在开腹肝切除中的镇痛效果比较[J]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 189-194.
[11] 史亚波, 李扬, 黄长文. 缺血-再灌注损伤促进肝癌复发机制的研究进展[J]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 96-99.
[12] 戴伟川, 郭协力, 方仲宁, 蔡文华, 洪天生, 田夏阳. 显微镜下周围神经松解术治疗腰椎间盘突出症术后残余神经症状的疗效分析[J]. 中华神经创伤外科电子杂志, 2024, 10(02): 84-90.
[13] 李秀玲, 连少锋, 荣刘涛, 李登峰, 饶蕴玉. 利巴韦林联合复方嗜酸乳杆菌治疗轮状病毒肠炎患儿的临床研究[J]. 中华消化病与影像杂志(电子版), 2024, 14(04): 369-372.
[14] 吕涛, 张琨, 李晨. 芍黄安肠汤治疗重度活动期溃疡性结肠炎大肠湿热证患者的疗效及对肠黏膜屏障、炎症因子和免疫功能的影响[J]. 中华消化病与影像杂志(电子版), 2024, 14(01): 16-20.
[15] 屈霄, 王靓, 陆萍, 何斌, 孙敏. 外周血炎症因子及肠道菌群特征与活动性溃疡性结肠炎患者病情的相关性分析[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 466-470.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号