炎性小体在肺部疾病中的作用_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

王文连 , 林欣 ,  胡俊锋

蚌埠医学院第一附属医院呼吸与危重症学科（安徽蚌埠 233000）;

Corresponding author：

胡俊锋, Email: bbmchjf@126.com

Keywords：

DOI：

10.7507/1671-6205.201805056

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Citation： 王文连, 林欣, 胡俊锋. 炎性小体在肺部疾病中的作用. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(4): 404-408. doi: 10.7507/1671-6205.201805056 Copy

1.	Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol Cell, 2002, 10(2): 417-426.
2.	Boyden ED, Dietrich WF. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet, 2006, 38(2): 240-244.
3.	Elliott EI, Sutterwala FS. Initiation and perpetuation of NLRP3 inflammasome activation and assembly. Immunol Rev, 2015, 265(1): 35-52.
4.	Ozaki E, Campbell M, Doyle SL. Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives. J Inflamm Res, 2015, 8: 15-27.
5.	Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature, 2015, 526(7575): 660-665.
6.	Kopalli SR, Kang TB, Lee KH, et al. NLRP3 inflammasome activation inhibitors in inflammation-associated cancer immunotherapy: an update on the recent patents. Recent Pat Anticancer Drug Discov, 2018, 13(1): 106-117.
7.	Zhou R, Yazdi AS, Menu P, et al. A role for mitochondria in NLRP3 inflammasome activation. Nature, 2011, 469(7329): 221-225.
8.	Nichols RD, von Moltke J, Vance RE. NAIP/NLRC4 inflammasome activation in MRP8⁺ cells is sufficient to cause systemic inflammatory disease. Nat Commun, 2017, 8(1): 2209.
9.	Qu Y, Misaghi S, Newton K, et al. Dixit VM NLRP3 recruitment by NLRC4 during Salmonella infection. J Exp Med, 2016, 213(6): 877-885.
10.	De Young KL, Ray ME, Su YA, et al. Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma. Oncogene, 1997, 15(4): 453-457.
11.	Meunier E, Wallet P, Dreier RF, et al. Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida. Nat Immunol, 2015, 16(5): 476-484.
12.	Agostini L, Martinon F, Burns K, et al. NALP3 forms an IL-1β-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity, 2004, 20(3): 319-325.
13.	Kumar SR, Paudel S, Ghimire L, et al. Emerging roles of inflammasomes in acute pneumonia. Am J Respir Crit Care Med, 2018, 197(2): 160-171.
14.	Witzenrath M, Pache F, Lorenz D, et al. The NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host defense in pneumococcal pneumonia. J Immunol, 2011, 187(1): 434-440.
15.	Segovia JA, Chang TH, Winter VT, et al. NLRP3 is a critical regulator of inflammation and innate immune cell response during mycoplasma pneumoniae infection. Infect Immun, 2017, 86(1): e00548-17.
16.	Man SM, Hopkins LJ, Nugent E, et al. Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc Natl Acad Sci USA, 2014, 111(20): 7403-7408.
17.	Willingham SB, Allen IC, Bergstralh DT, et al. NLRP3 (NALP3, Cryopyrin) facilitates in vivo caspase-1 activation, necrosis, and HMGB1 release via inflammasome-dependent and -independent pathways. J Immunol, 2009, 183(3): 2008-2015.
18.	仝国辉, 李煜, 郑德生, 等. PM_2.5 通过激活 Nlrp3 炎性小体诱导小鼠肺炎症反应. 毒理学杂志, 2017, 31(3): 176-181.
19.	Dikshit N, Kale SD, Khameneh HJ, et al. NLRP3 inflammasome pathway has a critical role in the host immunity against clinically relevant Acinetobacter baumannii pulmonary infection. Mucosal Immunol, 2018, 11(1): 257-272.
20.	Lee BH, Hwang DM, Palaniyar N, et al. Activation of P2X₇ receptor by ATP plays an important role in regulating inflammatory responses during acute viral infection. PLoS One, 2012, 7(4): e35812.
21.	Lee S, Nakahira K, Dalli J, et al. NLRP3 inflammasome deficiency protects against microbial sepsis via increased lipoxin B4 synthesis. Am J Respir Crit Care Med, 2017, 196(6): 713-726.
22.	Kong H, Wang Y, Zeng X, et al. Differential expression of inflammasomes in lung cancer cell lines and tissues. Tumour Biol, 2015, 36(10): 7501-7513.
23.	Wang Y, Kong H, Zeng X, et al. Activation of NLRP3 inflammasome enhances the proliferation and migration of A549 lung cancer cells. Oncol Rep, 2016, 35(4): 2053-2064.
24.	Wang L, Zhang LF, Wu J, et al. IL-1β-mediated repression of microRNA-101 is crucial for inflammation-promoted lung tumorigenesis. Cancer Res, 2014, 74(17): 4720-4730.
25.	Terlizzi M, Colarusso C, Popolo A, et al. IL-1α and IL-1β-producing macrophages populate lung tumor lesions in mice. Oncotarget, 2016, 7(36): 58181-58192.
26.	Ridker PM, MacFadyen JG, Thuren T, et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet, 2017, 390(10105): 1833-1842.
27.	Timperi E, Focaccetti C, Gallerano D, et al. IL-18 receptor marks functional CD8T cells in non-small cell lung cancer. Oncoimmunology, 2017, 6(7): e1328337.
28.	Rovina N, Hillas G, Dima E, et al. VEGF and IL-18 in induced sputum of lung cancer patients. Cytokine, 2011, 54(3): 277-281.
29.	Pouwels SD, Zijlstra GJ, van der Toorn M, et al. Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice. Am J Physiol Lung Cell Mol Physiol, 2016, 310(4): 377-386.
30.	Mortaz E, Henricks PA, Kraneveld AD, et al. Cigarette smoke induces the release of CXCL-8 from human bronchial epithelial cells via TLRs and induction of the inflammasome. Biochim Biophys Acta, 2011, 1812(9): 1104-1110.
31.	Pauwels NS, Bracke KR, Dupont LL, et al. Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD. Eur Respir J, 2011, 38(5): 1019-1028.
32.	Eltom S, Belvisi MG, Stevenson CS, et al. Role of the inflammasome-caspase1/11-IL-1/18 axis in cigarette smoke driven airway inflammation: an insight into the pathogenesis of COPD. PLoS One, 2014, 9(11): e112829.
33.	武红莉, 田瑞雪, 宁兰丁, 等. 慢性阻塞性肺疾病患者肺部感染的影响因素分析及血清炎症因子水平变化分析. 中华医院感染学杂志, 2018, 28(1): 25-28.
34.	何子凡, 高岩, 王晓玲, 等. NLRP3 炎性小体在慢性阻塞性肺疾病患者机体炎症反应中作用的研究. 中国呼吸与危重监护杂志, 2018, 17(2): 119-123.
35.	Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med, 2005, 353(16): 1685-1693.
36.	刘泽玉, 姜宝珍, 杨志伟, 等. P-选择素糖蛋白配体在盐酸诱导小鼠急性肺损伤中的作用机制研究. 中国呼吸与危重监护杂志, 2017, 16(4): 394-400.
37.	Dolinay T, Kim YS, Howrylak J, et al. Inflammasome-regulated cytokines are critical mediators of acute lung injury. Am J Respir Crit Care Med, 2012, 185(11): 1225-1234.
38.	Mizushina Y, Shirasuna K, Usui F, et al. NLRP3 protein deficiency exacerbates hyperoxia-induced lethality through Stat3 protein signaling independent of interleukin-1β. J Biol Chem, 2015, 290(8): 5065-5077.
39.	Feng Z, Qi S, Zhang Y, et al. Ly6G+ neutrophil-derived miR-223 inhibits the NLRP3 inflammasome in mitochondrial DAMP-induced acute lung injury. Cell Death Dis, 2017, 8(11): e3170.
40.	Villegas LR, Kluck D, Field C, et al. Superoxide dismutase mimetic, MnTE-2-PyP, attenuates chronic hypoxia-induced pulmonary hypertension, pulmonary vascular remodeling, and activation of the NALP3 inflammasome. Antioxid Redox Signal, 2013, 18(14): 1753-1764.
41.	Cero FT, Hillestad V, Sjaastad I, et al. Absence of the inflammasome adaptor ASC reduces hypoxia-induced pulmonary hypertension in mice. Am J Physiol Lung Cell Mol Physiol, 2015, 309(4): 378-387.
42.	胡志, 马慧, 范粉玲, 等. ROS/ALOX5/NLRP3 信号通路激活在低氧所致肺动脉内皮增殖中的作用. 实用医院临床杂志, 2017, 14(6): 44-48.
43.	刘莹, 董文鹏, 陈长富, 等. 粉防己碱对肺动脉高压大鼠中 NLRP3 炎性小体表达研究. 临床心血管病杂志, 2017, 33(11): 1102-1106.
44.	Sayan M, Mossman BT. The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases. Part Fibre Toxicol, 2016, 13(1): 51.
45.	Wilson MS, Madala SK, Ramalingam TR, et al. Bleomycin and IL-1beta-mediated pulmonary fibrosis is IL-17A dependent. J Exp Med, 2010, 207(3): 535-552.
46.	Stout-Delgado HW, Cho SJ, Chu SG, et al. Age-dependent susceptibility to pulmonary fibrosis is associated with NLRP3 inflammasome activation. Am J Respir Cell Mol Biol, 2016, 55(2): 252-263.
47.	Artlett CM. The role of the NLRP3 inflammasome in fibrosis. Open Rheumatol J, 2012, 6(1): 80-86.
48.	Lorenz G, Darisipudi MN, Anders HJ. Canonical and non-canonical effects of the NLRP3 inflammasome in kidney inflammation and fibrosis. Nephrol Dial Transplant, 2014, 29(1): 41-48.
49.	Leal VNC, Genov IR, Mallozi MC, et al. Polymorphisms in inflammasome genes and risk of asthma in Brazilian children. Mol Immunol, 2018, 93: 64-67.
50.	Zhang JH, Chen YP, Yang X, et al. Vitamin D3 levels and NLRP3 expression in murine models of obese asthma: association with asthma outcomes. Braz J Med Biol Res, 2017, 51(1): e6841.
51.	Triantafilou K, Kar S, van Kuppeveld FJ, et al. Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells. Am J Respir Cell Mol Biol, 2013, 49(6): 923-934.
52.	Menzel M, Akbarshahi H, Mahmutovic Persson I, et al. Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model. ERJ Open Res, 2017, 3(4): 00047-2017.
53.	Liu Y, Gao X, Miao Y, et al. NLRP3 regulates macrophage M2 polarization through up-regulation of IL-4 in asthma. Biochem J, 2018, 475(12): 1995-2008.

1. Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol Cell, 2002, 10(2): 417-426.
2. Boyden ED, Dietrich WF. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet, 2006, 38(2): 240-244.
3. Elliott EI, Sutterwala FS. Initiation and perpetuation of NLRP3 inflammasome activation and assembly. Immunol Rev, 2015, 265(1): 35-52.
4. Ozaki E, Campbell M, Doyle SL. Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives. J Inflamm Res, 2015, 8: 15-27.
5. Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature, 2015, 526(7575): 660-665.
6. Kopalli SR, Kang TB, Lee KH, et al. NLRP3 inflammasome activation inhibitors in inflammation-associated cancer immunotherapy: an update on the recent patents. Recent Pat Anticancer Drug Discov, 2018, 13(1): 106-117.
7. Zhou R, Yazdi AS, Menu P, et al. A role for mitochondria in NLRP3 inflammasome activation. Nature, 2011, 469(7329): 221-225.
8. Nichols RD, von Moltke J, Vance RE. NAIP/NLRC4 inflammasome activation in MRP8⁺ cells is sufficient to cause systemic inflammatory disease. Nat Commun, 2017, 8(1): 2209.
9. Qu Y, Misaghi S, Newton K, et al. Dixit VM NLRP3 recruitment by NLRC4 during Salmonella infection. J Exp Med, 2016, 213(6): 877-885.
10. De Young KL, Ray ME, Su YA, et al. Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma. Oncogene, 1997, 15(4): 453-457.
11. Meunier E, Wallet P, Dreier RF, et al. Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida. Nat Immunol, 2015, 16(5): 476-484.
12. Agostini L, Martinon F, Burns K, et al. NALP3 forms an IL-1β-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity, 2004, 20(3): 319-325.
13. Kumar SR, Paudel S, Ghimire L, et al. Emerging roles of inflammasomes in acute pneumonia. Am J Respir Crit Care Med, 2018, 197(2): 160-171.
14. Witzenrath M, Pache F, Lorenz D, et al. The NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host defense in pneumococcal pneumonia. J Immunol, 2011, 187(1): 434-440.
15. Segovia JA, Chang TH, Winter VT, et al. NLRP3 is a critical regulator of inflammation and innate immune cell response during mycoplasma pneumoniae infection. Infect Immun, 2017, 86(1): e00548-17.
16. Man SM, Hopkins LJ, Nugent E, et al. Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc Natl Acad Sci USA, 2014, 111(20): 7403-7408.
17. Willingham SB, Allen IC, Bergstralh DT, et al. NLRP3 (NALP3, Cryopyrin) facilitates in vivo caspase-1 activation, necrosis, and HMGB1 release via inflammasome-dependent and -independent pathways. J Immunol, 2009, 183(3): 2008-2015.
18. 仝国辉, 李煜, 郑德生, 等. PM_2.5 通过激活 Nlrp3 炎性小体诱导小鼠肺炎症反应. 毒理学杂志, 2017, 31(3): 176-181.
19. Dikshit N, Kale SD, Khameneh HJ, et al. NLRP3 inflammasome pathway has a critical role in the host immunity against clinically relevant Acinetobacter baumannii pulmonary infection. Mucosal Immunol, 2018, 11(1): 257-272.
20. Lee BH, Hwang DM, Palaniyar N, et al. Activation of P2X₇ receptor by ATP plays an important role in regulating inflammatory responses during acute viral infection. PLoS One, 2012, 7(4): e35812.
21. Lee S, Nakahira K, Dalli J, et al. NLRP3 inflammasome deficiency protects against microbial sepsis via increased lipoxin B4 synthesis. Am J Respir Crit Care Med, 2017, 196(6): 713-726.
22. Kong H, Wang Y, Zeng X, et al. Differential expression of inflammasomes in lung cancer cell lines and tissues. Tumour Biol, 2015, 36(10): 7501-7513.
23. Wang Y, Kong H, Zeng X, et al. Activation of NLRP3 inflammasome enhances the proliferation and migration of A549 lung cancer cells. Oncol Rep, 2016, 35(4): 2053-2064.
24. Wang L, Zhang LF, Wu J, et al. IL-1β-mediated repression of microRNA-101 is crucial for inflammation-promoted lung tumorigenesis. Cancer Res, 2014, 74(17): 4720-4730.
25. Terlizzi M, Colarusso C, Popolo A, et al. IL-1α and IL-1β-producing macrophages populate lung tumor lesions in mice. Oncotarget, 2016, 7(36): 58181-58192.
26. Ridker PM, MacFadyen JG, Thuren T, et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet, 2017, 390(10105): 1833-1842.
27. Timperi E, Focaccetti C, Gallerano D, et al. IL-18 receptor marks functional CD8T cells in non-small cell lung cancer. Oncoimmunology, 2017, 6(7): e1328337.
28. Rovina N, Hillas G, Dima E, et al. VEGF and IL-18 in induced sputum of lung cancer patients. Cytokine, 2011, 54(3): 277-281.
29. Pouwels SD, Zijlstra GJ, van der Toorn M, et al. Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice. Am J Physiol Lung Cell Mol Physiol, 2016, 310(4): 377-386.
30. Mortaz E, Henricks PA, Kraneveld AD, et al. Cigarette smoke induces the release of CXCL-8 from human bronchial epithelial cells via TLRs and induction of the inflammasome. Biochim Biophys Acta, 2011, 1812(9): 1104-1110.
31. Pauwels NS, Bracke KR, Dupont LL, et al. Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD. Eur Respir J, 2011, 38(5): 1019-1028.
32. Eltom S, Belvisi MG, Stevenson CS, et al. Role of the inflammasome-caspase1/11-IL-1/18 axis in cigarette smoke driven airway inflammation: an insight into the pathogenesis of COPD. PLoS One, 2014, 9(11): e112829.
33. 武红莉, 田瑞雪, 宁兰丁, 等. 慢性阻塞性肺疾病患者肺部感染的影响因素分析及血清炎症因子水平变化分析. 中华医院感染学杂志, 2018, 28(1): 25-28.
34. 何子凡, 高岩, 王晓玲, 等. NLRP3 炎性小体在慢性阻塞性肺疾病患者机体炎症反应中作用的研究. 中国呼吸与危重监护杂志, 2018, 17(2): 119-123.
35. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med, 2005, 353(16): 1685-1693.
36. 刘泽玉, 姜宝珍, 杨志伟, 等. P-选择素糖蛋白配体在盐酸诱导小鼠急性肺损伤中的作用机制研究. 中国呼吸与危重监护杂志, 2017, 16(4): 394-400.
37. Dolinay T, Kim YS, Howrylak J, et al. Inflammasome-regulated cytokines are critical mediators of acute lung injury. Am J Respir Crit Care Med, 2012, 185(11): 1225-1234.
38. Mizushina Y, Shirasuna K, Usui F, et al. NLRP3 protein deficiency exacerbates hyperoxia-induced lethality through Stat3 protein signaling independent of interleukin-1β. J Biol Chem, 2015, 290(8): 5065-5077.
39. Feng Z, Qi S, Zhang Y, et al. Ly6G+ neutrophil-derived miR-223 inhibits the NLRP3 inflammasome in mitochondrial DAMP-induced acute lung injury. Cell Death Dis, 2017, 8(11): e3170.
40. Villegas LR, Kluck D, Field C, et al. Superoxide dismutase mimetic, MnTE-2-PyP, attenuates chronic hypoxia-induced pulmonary hypertension, pulmonary vascular remodeling, and activation of the NALP3 inflammasome. Antioxid Redox Signal, 2013, 18(14): 1753-1764.
41. Cero FT, Hillestad V, Sjaastad I, et al. Absence of the inflammasome adaptor ASC reduces hypoxia-induced pulmonary hypertension in mice. Am J Physiol Lung Cell Mol Physiol, 2015, 309(4): 378-387.
42. 胡志, 马慧, 范粉玲, 等. ROS/ALOX5/NLRP3 信号通路激活在低氧所致肺动脉内皮增殖中的作用. 实用医院临床杂志, 2017, 14(6): 44-48.
43. 刘莹, 董文鹏, 陈长富, 等. 粉防己碱对肺动脉高压大鼠中 NLRP3 炎性小体表达研究. 临床心血管病杂志, 2017, 33(11): 1102-1106.
44. Sayan M, Mossman BT. The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases. Part Fibre Toxicol, 2016, 13(1): 51.
45. Wilson MS, Madala SK, Ramalingam TR, et al. Bleomycin and IL-1beta-mediated pulmonary fibrosis is IL-17A dependent. J Exp Med, 2010, 207(3): 535-552.
46. Stout-Delgado HW, Cho SJ, Chu SG, et al. Age-dependent susceptibility to pulmonary fibrosis is associated with NLRP3 inflammasome activation. Am J Respir Cell Mol Biol, 2016, 55(2): 252-263.
47. Artlett CM. The role of the NLRP3 inflammasome in fibrosis. Open Rheumatol J, 2012, 6(1): 80-86.
48. Lorenz G, Darisipudi MN, Anders HJ. Canonical and non-canonical effects of the NLRP3 inflammasome in kidney inflammation and fibrosis. Nephrol Dial Transplant, 2014, 29(1): 41-48.
49. Leal VNC, Genov IR, Mallozi MC, et al. Polymorphisms in inflammasome genes and risk of asthma in Brazilian children. Mol Immunol, 2018, 93: 64-67.
50. Zhang JH, Chen YP, Yang X, et al. Vitamin D3 levels and NLRP3 expression in murine models of obese asthma: association with asthma outcomes. Braz J Med Biol Res, 2017, 51(1): e6841.
51. Triantafilou K, Kar S, van Kuppeveld FJ, et al. Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells. Am J Respir Cell Mol Biol, 2013, 49(6): 923-934.
52. Menzel M, Akbarshahi H, Mahmutovic Persson I, et al. Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model. ERJ Open Res, 2017, 3(4): 00047-2017.
53. Liu Y, Gao X, Miao Y, et al. NLRP3 regulates macrophage M2 polarization through up-regulation of IL-4 in asthma. Biochem J, 2018, 475(12): 1995-2008.

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