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NLRP3 Regulated CXCL12 Expression in Acute Neutrophilic Lung Injury.
Journal of Inflammation Research ( IF 4.2 ) Pub Date : 2020-07-23 , DOI: 10.2147/jir.s259633 Yanwen Peng 1 , Qiongli Wu 2 , Hao Tang 3 , Jingrou Chen 1 , Qili Wu 1 , Xiaofeng Yuan 4 , Shiqiu Xiong 5 , Yujin Ye 6 , Haijin Lv 7
Journal of Inflammation Research ( IF 4.2 ) Pub Date : 2020-07-23 , DOI: 10.2147/jir.s259633 Yanwen Peng 1 , Qiongli Wu 2 , Hao Tang 3 , Jingrou Chen 1 , Qili Wu 1 , Xiaofeng Yuan 4 , Shiqiu Xiong 5 , Yujin Ye 6 , Haijin Lv 7
Affiliation
Background and Purpose: Both NLRP3 inflammasome and chemokines are involved in the initiation and development of acute lung inflammation, but the underlying mechanism is still elusive. The present study investigated the role of chemokines and NLRP3 in recruiting neutrophils in the early phase of acute lung injury.
Methods: In an endotoxin (lipopolysaccharide [LPS])-induced acute lung injury model, we measured the lung injury severity, myeloperoxidase (MPO) activity and chemokine profiles in wild-type (WT) and NLRP3 knockout (NLRP3–/–) mice, and then identified the key chemokines by specific antibody blockage.
Results: The results showed that NLRP3 deficiency was associated with alleviating lung damage, by reducing alveolar epithelial cell apoptosis and decreasing neutrophil accumulation. Furthermore, compared with WT mice, IL-1β, CCL2, CXCL1, CXCL5 and CXCL12 levels from the serum of NLRP3–/– mice were much lower after exposure to LPS. However, in lung tissue, only lower CXCL12 levels were observed from the NLRP3–/– ALI mice, and higher levels of CXCR4 were expressed in NLRP3–/– neutrophils. Blockage of CXCL12 dramatically relieved the severity of ALI and reduced neutrophil accumulation in the lung.
Conclusion: NLRP3 alters CXCL12 expression in acute lung injury. CXCL12 is crucial for neutrophil recruitment in NLRP3-mediated neutrophilic lung injury.
Keywords: NLRP3, acute lung injury, ALI, neutrophils, chemokines, CXCL12
中文翻译：
NLRP3 调节急性中性粒细胞肺损伤中的 CXCL12 表达。
背景与目的： NLRP3 炎症小体和趋化因子均参与急性肺部炎症的发生和发展，但其潜在机制仍不清楚。本研究调查了趋化因子和 NLRP3 在急性肺损伤早期募集中性粒细胞中的作用。
方法：在内毒素（脂多糖 [LPS]）诱导的急性肺损伤模型中，我们测量了野生型 (WT) 和 NLRP3 敲除 (NLRP3 –/– ) 小鼠的肺损伤严重程度、髓过氧化物酶 (MPO) 活性和趋化因子谱，然后通过特异性抗体阻断鉴定关键趋化因子。
结果：结果表明，NLRP3 缺乏与减轻肺损伤有关，通过减少肺泡上皮细胞凋亡和减少中性粒细胞积累。此外，与 WT 小鼠相比，暴露于 LPS 后，NLRP3 –/–小鼠血清中的 IL-1β、CCL2、CXCL1、CXCL5 和 CXCL12 水平要低得多。然而，在肺组织中，NLRP3 –/– ALI 小鼠仅观察到较低的 CXCL12 水平，而 NLRP3 –/–中性粒细胞中表达的 CXCR4 水平较高。CXCL12 的阻断显着减轻了 ALI 的严重程度并减少了肺中的中性粒细胞积聚。
结论：NLRP3 改变急性肺损伤中 CXCL12 的表达。CXCL12 对 NLRP3 介导的中性粒细胞肺损伤中的中性粒细胞募集至关重要。
关键词： NLRP3，急性肺损伤，ALI，中性粒细胞，趋化因子，CXCL12
更新日期：2020-07-23
Methods: In an endotoxin (lipopolysaccharide [LPS])-induced acute lung injury model, we measured the lung injury severity, myeloperoxidase (MPO) activity and chemokine profiles in wild-type (WT) and NLRP3 knockout (NLRP3–/–) mice, and then identified the key chemokines by specific antibody blockage.
Results: The results showed that NLRP3 deficiency was associated with alleviating lung damage, by reducing alveolar epithelial cell apoptosis and decreasing neutrophil accumulation. Furthermore, compared with WT mice, IL-1β, CCL2, CXCL1, CXCL5 and CXCL12 levels from the serum of NLRP3–/– mice were much lower after exposure to LPS. However, in lung tissue, only lower CXCL12 levels were observed from the NLRP3–/– ALI mice, and higher levels of CXCR4 were expressed in NLRP3–/– neutrophils. Blockage of CXCL12 dramatically relieved the severity of ALI and reduced neutrophil accumulation in the lung.
Conclusion: NLRP3 alters CXCL12 expression in acute lung injury. CXCL12 is crucial for neutrophil recruitment in NLRP3-mediated neutrophilic lung injury.
Keywords: NLRP3, acute lung injury, ALI, neutrophils, chemokines, CXCL12
中文翻译：
NLRP3 调节急性中性粒细胞肺损伤中的 CXCL12 表达。
背景与目的： NLRP3 炎症小体和趋化因子均参与急性肺部炎症的发生和发展，但其潜在机制仍不清楚。本研究调查了趋化因子和 NLRP3 在急性肺损伤早期募集中性粒细胞中的作用。
方法：在内毒素（脂多糖 [LPS]）诱导的急性肺损伤模型中，我们测量了野生型 (WT) 和 NLRP3 敲除 (NLRP3 –/– ) 小鼠的肺损伤严重程度、髓过氧化物酶 (MPO) 活性和趋化因子谱，然后通过特异性抗体阻断鉴定关键趋化因子。
结果：结果表明，NLRP3 缺乏与减轻肺损伤有关，通过减少肺泡上皮细胞凋亡和减少中性粒细胞积累。此外，与 WT 小鼠相比，暴露于 LPS 后，NLRP3 –/–小鼠血清中的 IL-1β、CCL2、CXCL1、CXCL5 和 CXCL12 水平要低得多。然而，在肺组织中，NLRP3 –/– ALI 小鼠仅观察到较低的 CXCL12 水平，而 NLRP3 –/–中性粒细胞中表达的 CXCR4 水平较高。CXCL12 的阻断显着减轻了 ALI 的严重程度并减少了肺中的中性粒细胞积聚。
结论：NLRP3 改变急性肺损伤中 CXCL12 的表达。CXCL12 对 NLRP3 介导的中性粒细胞肺损伤中的中性粒细胞募集至关重要。
关键词： NLRP3，急性肺损伤，ALI，中性粒细胞，趋化因子，CXCL12
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