The role of NLRP3 inflammasome in inflammatory response in patients with chronic obstructive pulmonary disease_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

HE Zifan , GAO Yan , WANG Xiaoling , XU Xilin ,  LIU Dong ,  LU Xianling

First Department of Respiratory Medicine, The First Affiliated Hospital of Shihezi Medical University, Shihezi, Xinjiang 832000, P. R. China;

Corresponding author：

LIU Dong, Email: 13779702431@163.com; LU Xianling, Email: luxianlingmary@163.com

Keywords：

Chronic obstructive pulmonary disease; NLRP3 inflammasome; IL-18; IL-1β; Peripheral blood mononuclear cells

DOI：

10.7507/1671-6205.201707043

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Objective To study the expression of NLRP3 inflammasome and its downstream inflammatory factors in patients with chronic obstructive pulmonary disease (COPD) and healthy controls, and to reveal the effect and significance of NLRP3 inflammasome in the pathogenesis of COPD. Methods Forty patients with acute exacerbation COPD (AECOPD) who were hospitalized from November 2016 to May 2017 were recruited in the AECOPD group, and recruited in the stable COPD group when they entered the stable stage. Forty healthy individuals were recruited in the control group. General information and peripheral blood were collected from each subject. The levels of NLRP3 mRNA and caspase-1 mRNA in peripheral blood mononuclear cells were measured by real-time PCR. The levels of IL-18 and IL-1β were measured by enzyme-linked immunosorbent assay. Results The levels of NLRP3 mRNA, IL-18 and IL-1β in the AECOPD patients were significantly higher than those in the stable COPD group [2.11±0.77, 12.79 (7.10, 43.13) pg/ml, 17.02 (8.36, 52.21) pg/ml vs. 1.60±0.44, 10.66 (6.32, 18.59) pg/ml, 13.34 (7.07, 16.89) pg/ml, all P<0.05] . The levels of NLRP3 mRNA, IL-18 and IL-1β in the AECOPD patients were significantly higher than those in the control group [2.11±0.77, 12.79 (7.10, 43.13) pg/ml, 17.02 (8.36, 52.21) pg/mlvs. 1.00±0.49, 6.29 (4.73, 7.93) pg/ml, 5.93 (4.81, 9.67) pg/ml, all P<0.05]. The levels of NLRP3 mRNA, IL-18 and IL-1β were significantly higher in the stable COPD group than the control group [1.60±0.44, 10.66 (6.32, 18.59) pg/ml, 13.34 (7.07, 16.89) pg/mlvs. (1.00±0.49, 6.29 (4.73, 7.93) pg/ml, 5.93 (4.81, 9.67) pg/ml, all P<0.05]. Correlation analysis showed that the plasma IL-18 level was positive correlated with leukocyte count and neutrophil percentage in the AECOPD group (r=0.372, P<0.05;r=0.386, P<0.05). The expression of NLRP3 mRNA in the AECOPD group and stable COPD group were positively correlated with the CAT score (r=0.387, P<0.05;r=0.399, P<0.05) . Conclusion NLRP3 inflammasome is involved in the inflammatory response in COPD patients.

Citation： HE Zifan, GAO Yan, WANG Xiaoling, XU Xilin, LIU Dong, LU Xianling. The role of NLRP3 inflammasome in inflammatory response in patients with chronic obstructive pulmonary disease. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(2): 119-123. doi: 10.7507/1671-6205.201707043 Copy

1.	Global Strategy for the Diagnosis, Management and Preventionof COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). updated 2016. http://goldcopd.org/.
2.	Howrylak JA, Nakahira K.Inflammasomes: Key mediators of lung Immunity. Annu Rev Physiol, 2017, 79: 471-494.
3.	Martinon F, Agostini L, Meylan E, et al. Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr Biol, 2004, 14(21): 1929-1934.
4.	Kanneganti TD, Ozören N, Body-Malapel M, et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature, 2006, 440(7081): 233-236.
5.	Kanneganti TD, Body-Malapel M, Amer A, et al. Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J Biol Chem, 2006, 281(48): 36560-36568.
6.	Riteau N, Gasse P, FAUConnier L, et al. Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am J Respir Crit Care Med, 2010, 182(6): 774-783.
7.	Gross O, Thomas CJ, Guarda G, et al. The inflammasome: an integrated view. Immunol Rev, 2011, 243(1): 136-151.
8.	Faner R, Sobradillo P, Noguera A, et al. The inflammasome pathway in stable COPD and acute exacerbations.ERJ Open Res, 2016, 2(3), pii: 00002-2016.
9.	Di Stefano A, Caramori G, Barczyk A, et al. Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD. Thorax, 2014, 69(6): 516-524.
10.	马强, 吴占庆, 杨培雄, 李琳业.慢性阻塞性肺疾病患者血清白细胞介素表达及临床意义. 中国老年学杂志, 2016, 36(17): 4266-4267.
11.	鲍中未, 郭金兰.血清白介素-18、单核细胞趋化蛋白-1 和高敏 C 反应蛋白在慢性阻塞性肺疾病检测中的意义. 中外医学研究, 2017, 15(2): 8-11.
12.	孙世民, 张珠, 王云雀. COPD 急性加重期和稳定期血清炎性因子水平及其与肺功能的关系. 中国全科医学, 2014, 17(24): 2790-2793.
13.	Dima E, Koltsida O, Katsaounou P, et al. Implication of interleukin (IL)-18 in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cytokine, 2015, 74(2): 313-317.
14.	Jordan JA, Guo RF, Yun EC, et al. Role of IL-18 in acute lung inflammation.J Immunol, 2001, 167(12): 7060-7068.
15.	Mankan AK, Dau T, Jenne D, Hornung V. The NLRP3/ASC/Caspase-1 axis regulates IL-1β processing in neutrophils. Eur J Immunol, 2012, 42(3): 710-715.
16.	陈庆芸, 谢灿茂, 黄白丽, 等. IL-18、IL-13 和 TNF-α 在慢性阻塞性肺疾病中的变化及意义. 中国现代医学杂志, 2011, 21(22): 2796-2799.
17.	Pinkerton JW, Kim RY, Robertson AAB, et al. Inflammasomes in the lung. Mol Immunol, 2017, 86: 44-55.

1. Global Strategy for the Diagnosis, Management and Preventionof COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). updated 2016. http://goldcopd.org/.
2. Howrylak JA, Nakahira K.Inflammasomes: Key mediators of lung Immunity. Annu Rev Physiol, 2017, 79: 471-494.
3. Martinon F, Agostini L, Meylan E, et al. Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr Biol, 2004, 14(21): 1929-1934.
4. Kanneganti TD, Ozören N, Body-Malapel M, et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature, 2006, 440(7081): 233-236.
5. Kanneganti TD, Body-Malapel M, Amer A, et al. Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J Biol Chem, 2006, 281(48): 36560-36568.
6. Riteau N, Gasse P, FAUConnier L, et al. Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am J Respir Crit Care Med, 2010, 182(6): 774-783.
7. Gross O, Thomas CJ, Guarda G, et al. The inflammasome: an integrated view. Immunol Rev, 2011, 243(1): 136-151.
8. Faner R, Sobradillo P, Noguera A, et al. The inflammasome pathway in stable COPD and acute exacerbations.ERJ Open Res, 2016, 2(3), pii: 00002-2016.
9. Di Stefano A, Caramori G, Barczyk A, et al. Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD. Thorax, 2014, 69(6): 516-524.
10. 马强, 吴占庆, 杨培雄, 李琳业.慢性阻塞性肺疾病患者血清白细胞介素表达及临床意义. 中国老年学杂志, 2016, 36(17): 4266-4267.
11. 鲍中未, 郭金兰.血清白介素-18、单核细胞趋化蛋白-1 和高敏 C 反应蛋白在慢性阻塞性肺疾病检测中的意义. 中外医学研究, 2017, 15(2): 8-11.
12. 孙世民, 张珠, 王云雀. COPD 急性加重期和稳定期血清炎性因子水平及其与肺功能的关系. 中国全科医学, 2014, 17(24): 2790-2793.
13. Dima E, Koltsida O, Katsaounou P, et al. Implication of interleukin (IL)-18 in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cytokine, 2015, 74(2): 313-317.
14. Jordan JA, Guo RF, Yun EC, et al. Role of IL-18 in acute lung inflammation.J Immunol, 2001, 167(12): 7060-7068.
15. Mankan AK, Dau T, Jenne D, Hornung V. The NLRP3/ASC/Caspase-1 axis regulates IL-1β processing in neutrophils. Eur J Immunol, 2012, 42(3): 710-715.
16. 陈庆芸, 谢灿茂, 黄白丽, 等. IL-18、IL-13 和 TNF-α 在慢性阻塞性肺疾病中的变化及意义. 中国现代医学杂志, 2011, 21(22): 2796-2799.
17. Pinkerton JW, Kim RY, Robertson AAB, et al. Inflammasomes in the lung. Mol Immunol, 2017, 86: 44-55.

Chinese Journal of Respiratory and Critical Care Medicine

The role of NLRP3 inflammasome in inflammatory response in patients with chronic obstructive pulmonary disease

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