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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2022年04期

页码:

468-472

栏目:

论著

出版日期:

2022-08-20

文章信息/Info

Title:

Expression of NLRP3 Inflammasome, TNF-α and HMGB1 in COPD Patients and Their Relationship

作者:

刘欣¹; 2; 李艳敏¹; 郑佳¹; 赵商岐¹; 唐晓慧¹; 赵静³; 周文涛³; 周晓涛¹

830011 乌鲁木齐,新疆医科大学基础医学院免疫学教研室¹ 831100 昌吉,新疆昌吉职业技术学院² 830011 乌鲁木齐,新疆医科大学第五附属医院呼吸科³

Author(s):

Liu Xin¹; 2;  Li Yanmin¹;  Zheng Jia¹;  Zhao Shangqi¹;  Tang Xiaohui¹;  Zhao Jing³;  Zhou Wentao¹;  Zhou Xiaotao².

¹Department of Immunology, Basic Medical College of the Xinjiang Medical University, Urumqi 830011, China; ²Xinjiang Changji Vocational and Technical College, Changji 831100, China; ³The Fifth Affilated Hospital of Xinjing Medical University, Urumqi 830011, China

关键词:

肺疾病; 慢性阻塞性;  NLRP3炎症小体;  肿瘤坏死因子-α;  人高迁移率族蛋白B1

Keywords:

Chronic obstructive pulmonary disease;  NLRP3 inflammatory corpuscle;  Tumor necrosis factor a;  Human high mobility group protein B1

分类号:

R563

DOI:

10.3877/cma.j.issn.1674-6902.2022.04.003

摘要:

目的 分析核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体通路,早期炎症因子肿瘤坏死因子α(TNF-α),人高迁移率族蛋白B1(HMGB1)在慢性阻塞性肺疾病急性加重期(AECOPD)患者中的表达及相关性。方法 选择2017年9月至2019年2月我院呼吸内科收治的AECOPD患者48例为观察组,健康者30例为对照组,采用实时荧光定量PCR技术检测NLRP3炎症小体组分NLRP3、ASC、Caspase1及其活化因子IL-1β、IL-18的mRNA表达,采用ELISA法检测血清中IL-1β、IL-18、TNF -α、HMGB1。结果 观察组NLRP3mRNA、IL-18mRNA表达水平高于对照组(P<0.05); 观察组血清中IL-1β、IL-18、TNF-α、HMGB1含量高于对照组(P<0.05); 观察组NLRP3mRNA表达与IL-18mRNA表达呈负相关(P<0.05); 血清中TNF-α、IL-1β、HMGB1之间表达呈正相关(P<0.05); 病程>10年患者Caspase1 mRNA、血清IL-18和TNF-α的水平高于病程≤10年患者(P<0.05); Caspase1 mRNA与病程不相关(P>0.05),血清中IL-18及TNF-α与病程正相关(P<0.05),确诊年龄,移动度(右)与病程负相关(P<0.05); 病程、移动度对Caspase1 mRNA不相关(P>0.05); 移动度对血清IL-18和TNF-α不相关(P>0.05),病程与血清IL-18和TNF-α呈正相关(P<0.01)。结论 NLRP3炎症小体相关指标、TNF-α及HMGB1参与AECOPD的炎症过程。血清中IL-1β、TNF-α和HMGB1可作为AECOPD的临床炎症诊断指标。病程越长,AECOPD体内Caspase1 mRNA、血清中TNF-α、IL-18含量越高,提示感染性炎症越明显。

Abstract:

Objective To explore the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome pathway, early inflammatory factor-tumor necrosis factor α(TNF-α), human high mobility group protein B1(HMGB1)in the patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and their relationship. Methods A total of 48 AECOPD patients admitted to the respiratory department of our hospital from September 2017 to February 2019 were selected as the observation group, and 30 healthy patients as the control group. The mRNA level of the NLRP3 inflammasome components(NLRP3, ASC, CASP1 and its activating factors IL-1β and IL-18)was detected by Real-time fluorescent quantitative PCR technology, serum was prepared to detect the concentration of IL-1β, IL-18, TNF-α and HMGB1 by ELISA. Results The expression levels of NLRP3mRNA and IL-18 mrna in observation group were higher than those in control group(P<0.05). The contents of IL-1β, IL-18, TNF-α and HMGB1 in serum of observation group were higher than those of control group(P<0.05). NLRP3mRNA expression was negatively correlated with IL-18 mrna expression in observation group(P<0.05); The expressions of TNF-α, IL-1β and HMGB1 in serum were positively correlated(P<0.05). The levels of caspase1mRNA, serum IL-18 and TNF-α in the course of disease > 10 years group were higher than those in the course of disease ≤10 years group(P<0.05). Caspase1mRNA was not correlated with the course of disease(P>0.05), serum IL-18 and TNF-α were positively correlated with the course of disease(P<0.05), age of diagnosis, degree of mobility(right)were negatively correlated with the course of disease(P<0.05). There was no correlation between course of disease and degree of movement on caspase1 mRNA(P>0.05). The degree of mobility was not correlated with serum IL-18 and TNF-α(P>0.05), but the course of disease was positively correlated with serum IL-18 and TNF-α(P<0.01). Conclusion NLRP3 inflammasome related indexes, TNF-α and HMGB1 are involved in the inflammatory process of AECOPD. Serum IL-1β, TNF-α and HMGB1 can be considered as clinical inflammatory diagnostic indicators of AECOPD. The longer the course of disease, the higher the contents of caspase1mRNA, TNF-α and IL-18 in serum of AECOPD patients, indicating the more obvious infectious inflammation.

参考文献/References:

1 任成山, 王关嵩, 钱桂生. 慢性阻塞性肺疾病的成因及其治疗的困惑与希望[J/CD]. 中华肺部疾病杂志(电子版), 2019, 12(2): 127-141.
2 Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global bueden of disease study[J]. Lancet,1997, 348(9064): 1498-1504.
3 Omar A, Ganapathy SS, Anuar MFM, et al. Cause-specific mortality estimates for Malaysia in 2013: results from a national sample verification study using medical record review and verbal autopsy[J]. BMC Public Health, 2019, 19(1): 110.
4 Lopez AD, Shibuya K, Rao C, et al. Chronic obstructive pulmonary disease: current burden and future projections[J]. Eur Respir, 2006, 27: 397-412.
5 Lakiang T, Nair NS, Ramaswamy A, et al. Economic impact of chronic obstructive pulmonary disease: A cross-sectional study at teaching hospital in South India[J]. J Family Med Prim Care, 2018, 7(5): 1002-1006.
6 Wang Xishuai, Wang Zhiqing, Tang Donghui. Aerobic exercise alleviates inflammation, oxidative Stress, and Apoptosis in Mice with Chronic Obstructive Pulmonary Disease[J]. Int J Chron Obstruct Pulmon Dis, 2021, 16: 1369-1379.
7 Qu Jiao, Yue Li, Gao Jian, et al. Perspectives on wnt signal pathway in the pathogenesis and therapeutics of chronic obstructive pulmonary disease[J]. J Pharmacol Exp Ther, 2019, 369: 473-480.
8 El Kharbili Manale, Aviszus Katja, Sasse Sarah K, et al. Macrophage programming is regulated by a cooperative interaction between fatty acid binding protein 5 and peroxisome proliferator-activated receptor γ[J]. FASEB J, 2022, 36: e22300.
9 Rosa Faner, Patricia Sobradillo, Aina Noguera, et al. The inflammasome pathway in stable COPD and acute exacerbations[J]. ERJ Open Res, 2016, 2(3): 00002-2016.
10 De Nardo D, De Nardo CM, Latz E. New insights into mechanisms controlling the NLRP3 inflammasome and its role in lung disease[J]. Am J Pathol, 2014, 184(1): 42-54.
11 Rovina N, Koutsoukou A, Koulouris NG. Inflammation and immune response in COPD: where do we stand[J]. Mediators Inflamm, 2013: 413735.
12 Pauwels NS, Bracke KR, Dupont LL, et al. Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD[J]. Eur Respir J, 2011, 38: 1019-1028.
13 Li C, Zhihong H, Wenlong L, et al. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome regulates bronchial epithelial cell injury and proapoptosis after exposure to biomass fuel smoke[J]. Am J Respir Cell Mol Biol, 2016, 55(6): 815-824.
14 Peng Z, Zhang W, Qiao J, et al. Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1β in rats with COPD[J]. Int Immunopharmacol, 2018, 62: 23-28.
15 Andreeva Liudmila, David Liron, Rawson Shaun, et al. NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation.[J]. Cell, 2021, 184: 6299-6312.
16 Lin Xin, Zhu Yong, Le Guohui, Tetramethylpyrazine Alleviates Tight Junction Disruption of Bronchial Mucosal Epithelial Cells Caused by Interleukin-17 via Inhibiting Nuclear Factor-κB-p65/Tumor Necrosis Factor-α Signaling Pathway.[J]. J Interferon Cytokine Res, 2021, 41: 415-424.
17 Malaviya Rama, Laskin Jeffrey D, Laskin Debra L, Anti-TNFα therapy in inflammatory lung diseases.[J]. Pharmacol Ther, 2017, 180: 90-98.
18 Niu Jiani, Cederstrand Annika J, Eddinger Geoffrey A, et al. Trimer-to-Monomer Disruption Mechanism for a Potent, Protease-Resistant Antagonist of Tumor Necrosis Factor-α Signaling[J]. J Am Chem Soc, 2022, undefined: undefined.
19 Jang Dan-In, Lee A-Hyeon, Shin Hye-Yoon, et al. The Role of Tumor Necrosis Factor Alpha(TNF-α)in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics.[J]. Int J Mol Sci, 2021, 22: undefined.
20 Gao Wei, Gao Lianjun, Yang Feng, et al. Circulating JNK pathway-associated phosphatase: A novel biomarker correlates with Th17 cells, acute exacerbation risk, and severity in chronic obstructive pulmonary disease patients.[J]. J Clin Lab Anal, 2022, 36: e24153.
21 Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword[J]. Nat Rev Immunol, 2009, 9(4): 271-285.
22 Mazur-Bialy Agnieszka Irena, Pochec Ewa, HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin.[J]. Arch Immunol Ther Exp(Warsz), 2016, 64: 171-176.
23 Dong Yuanji, Ming Bingxia, Dong Lingli, The Role of HMGB1 in Rheumatic Diseases.[J]. Front Immunol, 2022, 13: 815257.
24 Li M, Guo L, Wang H, et al. RAGE-ligands axis: A new 'driving force' for cigarette smoke-induced airway inflammation in COPD[J]. Respirology, 2015, 20(6): 998-999.
25 Zhang Y, Li S, Wang G, et al. Changes of HMGB1 and sRAGE during the recovery of COPD exacerbation[J]. Thorac Dis, 2014, 6: 734-741.
26 Wang Huijie, Zhong Yonghong, Li Na, et al. Transcriptomic analysis and validation reveal the pathogenesis and a novel biomarker of acute exacerbation of chronic obstructive pulmonary disease.[J]. Respir Res, 2022, 23: 27.
27 Levy Ilana, Elimeleh Yotam, Gavrieli Sagi, et al. Treatment of acute exacerbations of chronic obstructive pulmonary disease with acupuncture during hospitalization: a three-arm double-blinded randomized sham-controlled trial.[J]. Acupunct Med, 2022, undefined: 9645284221086293.
28 Shi Lin, Zhu Bijun, Xu Menglin, et al. Selection of AECOPD-specific immunomodulatory biomarkers by integrating genomics and proteomics with clinical informatics.[J]. Cell Biol Toxicol, 2018, 34: 109-123.
29 Li Xiaolong, Wu Zhen, Xue Mingyue, et al. Smoking status affects clinical characteristics and disease course of acute exacerbation of chronic obstructive pulmonary disease: A prospectively observational study.[J]. Chron Respir Dis, 2020, 17: 1479973120916184.
30 Kang MJ, Choi JM, Kim BH, et al. IL-18 induces emphysema and airway and vascular remodeling via IFN-γ, IL-17A, and IL-13[J]. Am J Respir Crit Care Med, 2012, 185(11): 1205-1217.

备注/Memo

备注/Memo:

基金项目: 国家自然科学基金资助项目(81760656); 新疆维吾尔自治区自然科学基金资助项目(2018D01C299)
通信作者: 周晓涛, Email: xiaotaozhou9@sina.com

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更新日期/Last Update: 2022-08-20