Abstract Objective To study the regulatory effect of the NOD-like receptor, pyrin domain-containing 3 (NLRP3) on airway inflammatory response and pyroptosis in mice with asthma. Methods The NLRP3 wild-type (WT) C57BL/6J mice were divided into two groups: NLRP3-WT control and NLRP3-WT asthma. The mice with NLRP3 knockout (KO) were divided into two groups: NLRP3-KO control and NLRP3-KO asthma (n=10 each). A model of asthma was prepared by intraperitoneal injection of ovalbumin + aluminium hydroxide for sensitization and ovalbumin inhalation for challenge. Enhanced pause, an index for airway responsiveness, was measured for each group. Hematoxylin and eosin staining was used to observe the histomorphological changes of lungs and determine the inflammation score for each group. Bronchoalveolar lavage fluid was collected from each group to determine the numbers of neutrophils, eosinophils, and lymphocytes and measure the content of interleukin-1β (IL-1β) and interleukin-18 (IL-18). Western blot was used to measure the expression of NLRP3, cleaved caspase-1, and Gasdermin D-N in lung tissue of each group. Results Compared with the NLRP3-WT control group, the NLRP3-WT asthma group showed morphological changes including airway smooth muscle thickening and inflammatory cell infiltration. Compared with the NLRP3-WT asthma group, the NLRP3-KO asthma group had significant improvements in the above morphological manifestations. Compared with the NLRP3-WT control group, the NLRP3-WT asthma group had significant increases in the enhanced pause, the inflammation score of lung tissue, the numbers of neutrophils, eosinophils and lymphocytes in bronchoalveolar lavage fluid, and the levels of IL-1β and IL-18 in bronchoalveolar lavage fluid (P<0.05). The expression of NLRP3, cleaved caspase-1, and Gasdermin D-N in lung tissue also significantly increased in the NLRP3-WT asthma group (P<0.05). The above indices in the NLRP3-KO asthma group were significantly lower than those in the NLRP3-WT asthma group (P<0.05). Conclusions The overexpression of NLRP3 is associated with the pathogenesis of asthma, which may be related to the molecular mechanisms of the activation of airway inflammatory response and pyroptosis. Citation:
Wang L, Lei W, Zhang SJ, et al. MCC950, a NLRP3 inhibitor, ameliorates lipopolysaccharide-induced lung inflammation in mice[J]. Bioorg Med Chem, 2021, 30: 115954. PMID: 33360197. DOI: 10.1016/j.bmc.2020.115954.
He DK, Xu N, Shao YR, et al. NLRP3 gene silencing ameliorates phosgene-induced acute lung injury in rats by inhibiting NLRP3 inflammasome and proinflammatory factors, but not anti-inflammatory factors[J]. J Toxicol Sci, 2020, 45(10): 625-637. PMID: 33012731. DOI: 10.2131/jts.45.625.
Kubysheva N, Boldina M, Eliseeva T, et al. Relationship of serum lev els of IL-17, IL-18, TNF-α, and lung function para- meters in patients with COPD, asthma-COPD overlap, and bronchial asthma[J]. Mediators Inflamm, 2020, 2020: 4652898. PMID: 32733164. PMCID: PMC7372292. DOI: 10.1155/2020/4652898.
Xu MM, Wang L, Wang MY, et al. Mitochondrial ROS and NLRP3 inflammasome in acute ozone-induced murine model of airway inflammation and bronchial hyperresponsiveness[J]. Free Radic Res, 2019, 53(7): 780-790. PMID: 31185753. DOI: 10.1080/10715762.2019.1630735.
Guan ML, Ma HL, Fan XY, et al. Dexamethasone alleviate allergic airway inflammation in mice by inhibiting the activation of NLRP3 inflammasome[J]. Int Immunopharmacol, 2020, 78: 106017. PMID: 31780368. DOI: 10.1016/j.intimp.2019.106017.
Zhu CM, Zhang LG, Liu ZM, et al. Atractylenolide III reduces NLRP3 inflammasome activation and Th1/Th2 imbalances in both in vitro and in vivo models of asthma[J]. Clin Exp Pharmacol Physiol, 2020, 47(8): 1360-1367. PMID: 32196713. DOI: 10.1111/1440-1681.13306.
Wood LG, Li Q, Scott HA, et al. Saturated fatty acids, obesity, and the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in asthmatic patients[J]. J Allergy Clin Immunol, 2019, 143(1): 305-315. PMID: 29857009. DOI: 10.1016/j.jaci.2018.04.037.
Malinczak CA, Schuler CF, Duran AJ, et al. NLRP3-inflammasome inhibition during respiratory virus infection abrogates lung immunopathology and long-term airway disease development[J]. Viruses, 2021, 13(4): 692. PMID: 33923693. PMCID: PMC8072578. DOI: 10.3390/v13040692.
Donovan C, Liu G, Shen S, et al. The role of the microbiome and the NLRP3 inflammasome in the gut and lung[J]. J Leukoc Biol, 2020, 108(3): 925-935. PMID: 33405294. DOI: 10.1002/JLB.3MR0720-472RR.
Zhuang J, Cui HY, Zhuang LL, et al. Bronchial epithelial pyroptosis promotes airway inflammation in a murine model of toluene diisocyanate-induced asthma[J]. Biomed Pharmacother, 2020, 125: 109925. PMID: 32014690. DOI: 10.1016/j.biopha.2020.109925.
[1]
WANG Hui-Min, LIU Chuan-He, LIU Chang-Shan, WANG Ying, HAN Zhi-Ying, SUN Xin, CHEN Xing, AN Shu-Hua, DUOLIKUN Muzhapaer, LU Ai-Ping, WANG Min, CHENG Yan, YIN Xiao-Mei, LIU Han-Min, WANG Hong, HUA Shan, DONG Li, HUANG Ying, JIANG Yi, XIONG Jian-Xin, DING Sheng-Gang, ZHAO Shun-Ying, WANG Jin-Rong, HUANG Gui-Min, MU Jing-Hui, CHEN Yu-Zhi. Efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children: a real-world study[J]. CJCP, 2021, 23(9): 877-881.
