炎性小体在急性肺损伤中的研究进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

李园莉 , 程梓荷 ,  王胜昱

西安医学院第一附属医院呼吸与危重症医学科（陕西西安 710077）;

Corresponding author：

王胜昱, Email: wangshengyu@yeah.net

Keywords：

DOI：

10.7507/1671-6205.202502090

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

1.	Gu W, Zeng Q, Wang X, et al. Acute lung injury and the NLRP3 inflammasome. J Inflamm Res, 2024, 17: 3801-3813.
2.	Wei T, Zhang C, Song Y. Molecular mechanisms and roles of pyroptosis in acute lung injury. Chin Med J (Engl), 2022, 135(20): 2417-2426.
3.	Li J, Ma W, Li G. Research Progress on the Pathogenesis of Acute Lung Injury (ALI). Medicinal Plant, 2024, 15(4): 122-128.
4.	Coll RC, Schroder K, Pelegrín P. NLRP3 and pyroptosis blockers for treating inflammatory diseases. Trends Pharmacol Sci, 2022, 43(8): 653-668.
5.	Chen J, Wang S, Fu R, et al. RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice. J Transl Med, 2018, 16(1): 233.
6.	Kahlenberg JM, Kang I. The clinicopathologic significance of inflammasome activation in autoimmune diseases. Arthritis Rheumatol, 2020, 72(3): 386-395.
7.	Howrylak JA, Nakahira K. Inflammasomes: Key Mediators of Lung Immunity. Annu Rev Physiol, 2017, 79(1): 471-494.
8.	Down KP, Nguyen H, Dorfleutner A, et al. An overview of the non-canonical inflammasome. Mol Aspects Med, 2020, 76: 100924.
9.	高志丹, 金娟, 黄翠萍. NLRP3炎性小体及其在急性肺损伤/急性呼吸窘迫综合征中的研究进展. 湖北科技学院学报(医学版), 2022, 36(2): 171-175.
10.	Huang Y, Xu W, Zhou R. NLRP3 inflammasome activation and cell death. Cell Mol Immunol, 2021, 18(9): 2114-2127.
11.	Paik S, Kim JK, Silwal P, et al. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell Mol Immunol, 2021, 18(5): 1141.
12.	Yang K, Wang X, Pan H, et al. The roles of AIM2 in neurodegenerative diseases: insights and therapeutic implications. Front Immunol, 2024, 15.
13.	赵培, 郭石平. 黑色素瘤缺乏因子2炎症小体在非感染性肺部疾病中的研究进展. 中国呼吸与危重监护杂志, 2025, 24(2): 147-152.
14.	Wang J, Li R, Peng Z, et al. HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signaling pathways. Int J Mol Med, 2020, 45(1): 61-80.
15.	Ohto U. Activation and regulation mechanisms of NOD-like receptors based on structural biology. Front Immunol, 2022, 13: 953530.
16.	Meade JJ, Stuart S, Neiman-Zenevich J, et al. Activation of the NLRP1B inflammasome by caspase-8. Commun Biol, 2024, 7: 1164.
17.	Wen H, Miao EA, Ting JP. Mechanisms of NOD-like Receptor-Associated Inflammasome Activation. Immunity, 2013, 39(3): 432-441.
18.	Fu J, Schroder K, Wu H. Mechanistic insights from inflammasome structures. Nat Rev Immunol, 2024, 24(7).
19.	Sundaram B, Kanneganti TD. Advances in Understanding Activation and Function of the NLRC4 Inflammasome. Int J Mol Sci, 2021, 22(3): 1048.
20.	Dolinay T, Kim Y S, Howrylak J, et al. Inflammasome-regulated cytokines are critical mediators of acute lung injury. American Journal of Respiratory and Critical Care Medicine, 2012, 185(11): 1225-1234.
21.	Huang Q, Le Y, Li S, et al. Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS). Respir Res, 2024, 25(1): 30.
22.	Oltra SS, Colomo S, Sin L, et al. Distinct GSDMB protein isoforms and protease cleavage processes differentially control pyroptotic cell death and mitochondrial damage in cancer cells. Cell Death Differ, 2023, 30(5): 1366-1381.
23.	Song H, Yang B, Li Y, et al. Focus on the mechanisms and functions of pyroptosis, inflammasomes, and inflammatory caspases in infectious diseases. Oxid Med Cell Longev, 2022, 2022: 2501279.
24.	Murao A, Aziz M, Wang H, et al. Release mechanisms of major DAMPs. Apoptosis, 2021, 26(3-4): 152-162.
25.	Li H, Li Y, Song C, et al. Neutrophil extracellular traps augmented alveolar macrophage pyroptosis via AIM2 inflammasome activation in LPS-induced ALI/ARDS. J Inflammation Res, 2021, Volume 14: 4839-4858.
26.	Zou S, Jie H, Han X, et al. The role of neutrophil extracellular traps in sepsis and sepsis-related acute lung injury. Int Immunopharmacol, 2023, 124(Pt A): 110436.
27.	Tian Y, Qu S, Alam HB, et al. Peptidylarginine deiminase 2 has potential as both a biomarker and therapeutic target of sepsis. JCI Insight, 2020, 5(20): e138873.
28.	Yang J, Zhao Y, Zhang P, et al. Hemorrhagic shock primes for lung vascular endothelial cell pyroptosis: role in pulmonary inflammation following LPS. Cell Death Dis, 2016, 7(9): e2363.
29.	Tian X, Sun H, Casbon AJ, et al. NLRP3 inflammasome mediates dormant neutrophil recruitment following sterile lung injury and protects against subsequent bacterial pneumonia in mice. Front Immunol, 2017, 8: 1337.
30.	欧海燕, 段娅娟, 陈兰. 外周血单核细胞NLRP3炎性小体对脓毒症急性肺损伤患者病情严重程度的诊断价值. 实用医学杂志, 2020, 36(3): 380-384.
31.	Corcoran SE, Halai R, Cooper MA. Pharmacological inhibition of the nod-like receptor family pyrin domain containing 3 inflammasome with MCC950. Pharmacol Rev, 2021, 73(3): 968-1000.
32.	Wang L, Lei W, Zhang S, et al. MCC950, a NLRP3 inhibitor, ameliorates lipopolysaccharide-induced lung inflammation in mice. Bioorgan Med Chem, 2021, 30: 115954.
33.	Ba X, Ye T, He Y, et al. Engineered macrophage membrane-coated nanoparticles attenuate calcium oxalate nephrocalcinosis-induced kidney injury by reducing oxidative stress and pyroptosis. Acta Biomater, 2025, 195: 479-495.
34.	李翔鹏, 李风森, 李争, 等. 甘露清瘟方对小鼠急性肺损伤的治疗作用及其机制. 解放军医学杂志, 2025: 1-12.
35.	Yang J, Yang J, Huang X, et al. Glibenclamide Alleviates LPS-Induced Acute Lung Injury through NLRP3 Inflammasome Signaling Pathway. Mediators Inflamm, 2022, 2022: 8457010.
36.	Lv H, Yuan X, Zhang J, et al. Heat shock preconditioning mesenchymal stem cells attenuate acute lung injury via reducing NLRP3 inflammasome activation in macrophages. Stem Cell Res Ther, 2021, 12(1): 290.
37.	Green JP, El-Sharkawy LY, Roth S, et al. Discovery of an inhibitor of DNA-driven inflammation that preferentially targets the AIM2 inflammasome. iScience, 2023, 26(5): 106758.
38.	Zhong FL, Robinson K, Teo DET, et al. Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding. J Biol Chem, 2018, 293(49): 18864-18878.
39.	Harapas CR, Robinson KS, Lay K, et al. DPP9 deficiency: an inflammasomopathy that can be rescued by lowering NLRP1/IL-1 signaling. Sci Immunol, 2022, 7(75): eabi4611.
40.	Huang Y, Han M, Shi Q, et al. Li, P HY-021068 alleviates cerebral ischemia-reperfusion injury by inhibiting NLRP1 inflammasome and restoring autophagy function in mice. Exp Neurol, 2024, 371: 114583.
41.	Sebastian-Valverde M, Wu H, Al Rahim M, et al. Discovery and characterization of small-molecule inhibitors of NLRP3 and NLRC4 inflammasomes. J Biol Chem, 2021, 296: 100597.
42.	Lin WW, Lu YC, Huang BC, et al. Selective activation of pro-anti-IL-1β antibody enhances specificity for autoinflammatory disorder therapy. Sci Rep, 2021, 11(1): 14846.
43.	Naveed Z, Sarwar M, Ali Z, et al. Anakinra treatment efficacy in reduction of inflammatory biomarkers in COVID‐19 patients: a meta‐analysis. J Clin Lab Anal, 2022, 36(6): e24434.
44.	Engeroff P, Belbézier A, Monsel A, et al. Anakinra reduces lung inflammation in experimental acute lung injury. Immun Inflamm Dis, 2022, 10(2): 123-129.
45.	Grein IH, Meneghetti TC, Pelajo CF, et al. Canakinumab for the treatment of different refractory autoinflammatory disorders. Pediatr Rheumatol, 2014, 12(Suppl 1): P244.
46.	Zhang LM, Zhang J, Zhang Y, et al. Interleukin-18 binding protein attenuates lipopolysaccharide-induced acute lung injury in mice via suppression NF-κB and activation Nrf2 pathway. Biochem Biophys Res Commun, 2018, 505(3): 837-842.
47.	Geerlinks AV, Dvorak AM; XIAP Deficiency Treatment Consortium. A case of XIAP deficiency successfully managed with tadekinig alfa (rhIL-18BP). J Clin Immunol, 2022, 42(4): 901-903.
48.	Jia X, Cao B, An Y, et al. Rapamycin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting IL-1β and IL-18 production. Int Immunopharmacol, 2019, 67: 211-219.

1. Gu W, Zeng Q, Wang X, et al. Acute lung injury and the NLRP3 inflammasome. J Inflamm Res, 2024, 17: 3801-3813.
2. Wei T, Zhang C, Song Y. Molecular mechanisms and roles of pyroptosis in acute lung injury. Chin Med J (Engl), 2022, 135(20): 2417-2426.
3. Li J, Ma W, Li G. Research Progress on the Pathogenesis of Acute Lung Injury (ALI). Medicinal Plant, 2024, 15(4): 122-128.
4. Coll RC, Schroder K, Pelegrín P. NLRP3 and pyroptosis blockers for treating inflammatory diseases. Trends Pharmacol Sci, 2022, 43(8): 653-668.
5. Chen J, Wang S, Fu R, et al. RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice. J Transl Med, 2018, 16(1): 233.
6. Kahlenberg JM, Kang I. The clinicopathologic significance of inflammasome activation in autoimmune diseases. Arthritis Rheumatol, 2020, 72(3): 386-395.
7. Howrylak JA, Nakahira K. Inflammasomes: Key Mediators of Lung Immunity. Annu Rev Physiol, 2017, 79(1): 471-494.
8. Down KP, Nguyen H, Dorfleutner A, et al. An overview of the non-canonical inflammasome. Mol Aspects Med, 2020, 76: 100924.
9. 高志丹, 金娟, 黄翠萍. NLRP3炎性小体及其在急性肺损伤/急性呼吸窘迫综合征中的研究进展. 湖北科技学院学报(医学版), 2022, 36(2): 171-175.
10. Huang Y, Xu W, Zhou R. NLRP3 inflammasome activation and cell death. Cell Mol Immunol, 2021, 18(9): 2114-2127.
11. Paik S, Kim JK, Silwal P, et al. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell Mol Immunol, 2021, 18(5): 1141.
12. Yang K, Wang X, Pan H, et al. The roles of AIM2 in neurodegenerative diseases: insights and therapeutic implications. Front Immunol, 2024, 15.
13. 赵培, 郭石平. 黑色素瘤缺乏因子2炎症小体在非感染性肺部疾病中的研究进展. 中国呼吸与危重监护杂志, 2025, 24(2): 147-152.
14. Wang J, Li R, Peng Z, et al. HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signaling pathways. Int J Mol Med, 2020, 45(1): 61-80.
15. Ohto U. Activation and regulation mechanisms of NOD-like receptors based on structural biology. Front Immunol, 2022, 13: 953530.
16. Meade JJ, Stuart S, Neiman-Zenevich J, et al. Activation of the NLRP1B inflammasome by caspase-8. Commun Biol, 2024, 7: 1164.
17. Wen H, Miao EA, Ting JP. Mechanisms of NOD-like Receptor-Associated Inflammasome Activation. Immunity, 2013, 39(3): 432-441.
18. Fu J, Schroder K, Wu H. Mechanistic insights from inflammasome structures. Nat Rev Immunol, 2024, 24(7).
19. Sundaram B, Kanneganti TD. Advances in Understanding Activation and Function of the NLRC4 Inflammasome. Int J Mol Sci, 2021, 22(3): 1048.
20. Dolinay T, Kim Y S, Howrylak J, et al. Inflammasome-regulated cytokines are critical mediators of acute lung injury. American Journal of Respiratory and Critical Care Medicine, 2012, 185(11): 1225-1234.
21. Huang Q, Le Y, Li S, et al. Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS). Respir Res, 2024, 25(1): 30.
22. Oltra SS, Colomo S, Sin L, et al. Distinct GSDMB protein isoforms and protease cleavage processes differentially control pyroptotic cell death and mitochondrial damage in cancer cells. Cell Death Differ, 2023, 30(5): 1366-1381.
23. Song H, Yang B, Li Y, et al. Focus on the mechanisms and functions of pyroptosis, inflammasomes, and inflammatory caspases in infectious diseases. Oxid Med Cell Longev, 2022, 2022: 2501279.
24. Murao A, Aziz M, Wang H, et al. Release mechanisms of major DAMPs. Apoptosis, 2021, 26(3-4): 152-162.
25. Li H, Li Y, Song C, et al. Neutrophil extracellular traps augmented alveolar macrophage pyroptosis via AIM2 inflammasome activation in LPS-induced ALI/ARDS. J Inflammation Res, 2021, Volume 14: 4839-4858.
26. Zou S, Jie H, Han X, et al. The role of neutrophil extracellular traps in sepsis and sepsis-related acute lung injury. Int Immunopharmacol, 2023, 124(Pt A): 110436.
27. Tian Y, Qu S, Alam HB, et al. Peptidylarginine deiminase 2 has potential as both a biomarker and therapeutic target of sepsis. JCI Insight, 2020, 5(20): e138873.
28. Yang J, Zhao Y, Zhang P, et al. Hemorrhagic shock primes for lung vascular endothelial cell pyroptosis: role in pulmonary inflammation following LPS. Cell Death Dis, 2016, 7(9): e2363.
29. Tian X, Sun H, Casbon AJ, et al. NLRP3 inflammasome mediates dormant neutrophil recruitment following sterile lung injury and protects against subsequent bacterial pneumonia in mice. Front Immunol, 2017, 8: 1337.
30. 欧海燕, 段娅娟, 陈兰. 外周血单核细胞NLRP3炎性小体对脓毒症急性肺损伤患者病情严重程度的诊断价值. 实用医学杂志, 2020, 36(3): 380-384.
31. Corcoran SE, Halai R, Cooper MA. Pharmacological inhibition of the nod-like receptor family pyrin domain containing 3 inflammasome with MCC950. Pharmacol Rev, 2021, 73(3): 968-1000.
32. Wang L, Lei W, Zhang S, et al. MCC950, a NLRP3 inhibitor, ameliorates lipopolysaccharide-induced lung inflammation in mice. Bioorgan Med Chem, 2021, 30: 115954.
33. Ba X, Ye T, He Y, et al. Engineered macrophage membrane-coated nanoparticles attenuate calcium oxalate nephrocalcinosis-induced kidney injury by reducing oxidative stress and pyroptosis. Acta Biomater, 2025, 195: 479-495.
34. 李翔鹏, 李风森, 李争, 等. 甘露清瘟方对小鼠急性肺损伤的治疗作用及其机制. 解放军医学杂志, 2025: 1-12.
35. Yang J, Yang J, Huang X, et al. Glibenclamide Alleviates LPS-Induced Acute Lung Injury through NLRP3 Inflammasome Signaling Pathway. Mediators Inflamm, 2022, 2022: 8457010.
36. Lv H, Yuan X, Zhang J, et al. Heat shock preconditioning mesenchymal stem cells attenuate acute lung injury via reducing NLRP3 inflammasome activation in macrophages. Stem Cell Res Ther, 2021, 12(1): 290.
37. Green JP, El-Sharkawy LY, Roth S, et al. Discovery of an inhibitor of DNA-driven inflammation that preferentially targets the AIM2 inflammasome. iScience, 2023, 26(5): 106758.
38. Zhong FL, Robinson K, Teo DET, et al. Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding. J Biol Chem, 2018, 293(49): 18864-18878.
39. Harapas CR, Robinson KS, Lay K, et al. DPP9 deficiency: an inflammasomopathy that can be rescued by lowering NLRP1/IL-1 signaling. Sci Immunol, 2022, 7(75): eabi4611.
40. Huang Y, Han M, Shi Q, et al. Li, P HY-021068 alleviates cerebral ischemia-reperfusion injury by inhibiting NLRP1 inflammasome and restoring autophagy function in mice. Exp Neurol, 2024, 371: 114583.
41. Sebastian-Valverde M, Wu H, Al Rahim M, et al. Discovery and characterization of small-molecule inhibitors of NLRP3 and NLRC4 inflammasomes. J Biol Chem, 2021, 296: 100597.
42. Lin WW, Lu YC, Huang BC, et al. Selective activation of pro-anti-IL-1β antibody enhances specificity for autoinflammatory disorder therapy. Sci Rep, 2021, 11(1): 14846.
43. Naveed Z, Sarwar M, Ali Z, et al. Anakinra treatment efficacy in reduction of inflammatory biomarkers in COVID‐19 patients: a meta‐analysis. J Clin Lab Anal, 2022, 36(6): e24434.
44. Engeroff P, Belbézier A, Monsel A, et al. Anakinra reduces lung inflammation in experimental acute lung injury. Immun Inflamm Dis, 2022, 10(2): 123-129.
45. Grein IH, Meneghetti TC, Pelajo CF, et al. Canakinumab for the treatment of different refractory autoinflammatory disorders. Pediatr Rheumatol, 2014, 12(Suppl 1): P244.
46. Zhang LM, Zhang J, Zhang Y, et al. Interleukin-18 binding protein attenuates lipopolysaccharide-induced acute lung injury in mice via suppression NF-κB and activation Nrf2 pathway. Biochem Biophys Res Commun, 2018, 505(3): 837-842.
47. Geerlinks AV, Dvorak AM; XIAP Deficiency Treatment Consortium. A case of XIAP deficiency successfully managed with tadekinig alfa (rhIL-18BP). J Clin Immunol, 2022, 42(4): 901-903.
48. Jia X, Cao B, An Y, et al. Rapamycin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting IL-1β and IL-18 production. Int Immunopharmacol, 2019, 67: 211-219.

Chinese Journal of Respiratory and Critical Care Medicine

Latest Articles炎性小体在急性肺损伤中的研究进展

Abstract Full text Figures/Tables Video References Cited by

Format

Content