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

doi:10.3877/cma.j.issn.1674-6902.2022.04.003

Abstract

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.

Key words: Chronic obstructive pulmonary disease, NLRP3 inflammatory corpuscle, Tumor necrosis factor a, Human high mobility group protein B1

Xin Liu, Yanmin Li, Jia Zheng, Shangqi Zhao, Xiaohui Tang, Jing Zhao, Wentao Zhou, Xiaotao Zhou. Expression of NLRP3 Inflammasome, TNF-α and HMGB1 in COPD Patients and Their Relationship[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2022, 15(04): 468-472.

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References 30

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炎症指标	对照组(n＝30)	观察组(n＝48)	t/U	P值
NLRP3(mRNA)	1.0±0.71	6.47±3.61	10.014	0.000
ASC(mRNA)	1.0±0.74	1.17±0.57	0.827	0.411
Caspase1(mRNA)	1.0±0.54	1.18±0.52	1.297	0.198
IL-1β(mRNA)	1.0±0.57	1.25±0.52	1.289	0.201
IL-18 (mRNA)	1.0±0.56	3.61±2.28	7.595	0.000
IL-1β(pg/ml)	8.64±1.10	12.23±2.43	7.609	0.000
IL-18(pg/ml)	115.86±20.31	185.60±45.63	9.226	0.000
TNF-α(pg/ml)	0.144	0.475	64.000	0.000
HMGB1(ng/ml)	5.68±0.35	8.95±1.48	14.668	0.000

炎症指标	对照组(n＝30)	观察组(n＝48)	t/U	P值
NLRP3(mRNA)	1.0±0.71	6.47±3.61	10.014	0.000
ASC(mRNA)	1.0±0.74	1.17±0.57	0.827	0.411
Caspase1(mRNA)	1.0±0.54	1.18±0.52	1.297	0.198
IL-1β(mRNA)	1.0±0.57	1.25±0.52	1.289	0.201
IL-18 (mRNA)	1.0±0.56	3.61±2.28	7.595	0.000
IL-1β(pg/ml)	8.64±1.10	12.23±2.43	7.609	0.000
IL-18(pg/ml)	115.86±20.31	185.60±45.63	9.226	0.000
TNF-α(pg/ml)	0.144	0.475	64.000	0.000
HMGB1(ng/ml)	5.68±0.35	8.95±1.48	14.668	0.000

临床资料	≤10年(n＝29)	>10年(n＝19)	t/U	P值
年龄	70.45±11.22	74.37±10.91	1.197	0.238
确诊疾病年龄	62.10±10.40	49.21±12.26	-3.913	0.000^b
脉搏(P)	86.86±14.83	87.74±13.32	0.208	0.836
呼吸(R)	20.52±0.91	21.00±1.45	1.418	0.163
移动度(左)	5.83±1.00	5.26±0.56	-2.493	0.016^a
移动度(右)	5.83±1.00	5.21±0.63	-2.387	0.021^a
烟龄	10.55±17.92	10.00±17.64	-0.105	0.917
NLRP3(mRNA)	0.16±3.75	6.93±3.43	0.713	0.479
ASC(mRNA)	1.21±0.60	1.11±0.52	-0.633	0.530
Caspase1(mRNA)	1.06±0.49	1.37±0.52	2.028	0.048^a
IL-1β(mRNA)	1.32±0.55	1.14±0.45	-1.192	0.239
IL -18(mRNA)	3.81±2.47	3.29±1.98	-0.769	0.446
IL-1β(pg/ml)	11.67±1.16	13.07±3.46	1.696	0.105
IL -18(pg/ml)	171.84±44.70	206.59±39.48	2.755	0.008^b
TNF-α(pg/ml)	0.371	0.494	127.000	0.002^b
HMGB1(ng/ml)	8.77±1.59	9.21±1.29	1.019	0.313

临床资料	≤10年(n＝29)	>10年(n＝19)	t/U	P值
年龄	70.45±11.22	74.37±10.91	1.197	0.238
确诊疾病年龄	62.10±10.40	49.21±12.26	-3.913	0.000^b
脉搏(P)	86.86±14.83	87.74±13.32	0.208	0.836
呼吸(R)	20.52±0.91	21.00±1.45	1.418	0.163
移动度(左)	5.83±1.00	5.26±0.56	-2.493	0.016^a
移动度(右)	5.83±1.00	5.21±0.63	-2.387	0.021^a
烟龄	10.55±17.92	10.00±17.64	-0.105	0.917
NLRP3(mRNA)	0.16±3.75	6.93±3.43	0.713	0.479
ASC(mRNA)	1.21±0.60	1.11±0.52	-0.633	0.530
Caspase1(mRNA)	1.06±0.49	1.37±0.52	2.028	0.048^a
IL-1β(mRNA)	1.32±0.55	1.14±0.45	-1.192	0.239
IL -18(mRNA)	3.81±2.47	3.29±1.98	-0.769	0.446
IL-1β(pg/ml)	11.67±1.16	13.07±3.46	1.696	0.105
IL -18(pg/ml)	171.84±44.70	206.59±39.48	2.755	0.008^b
TNF-α(pg/ml)	0.371	0.494	127.000	0.002^b
HMGB1(ng/ml)	8.77±1.59	9.21±1.29	1.019	0.313

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