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中华重症医学电子杂志 ›› 2019, Vol. 05 ›› Issue (01) : 46 -50. doi: 10.3877/cma.j.issn.2096-1537.2019.01.010

所属专题: 文献

综述

非经典途径细胞焦亡在脓毒症中的研究进展
彭菲1, 常炜1, 杨毅1,()   
  1. 1. 210009 南京,东南大学附属中大医院重症医学科
  • 收稿日期:2017-11-30 出版日期:2019-02-28
  • 通信作者: 杨毅
  • 基金资助:
    国家自然科学基金(81671892); 江苏省医学重点学科(实验室)(ZDXKA2016025); 江苏省医学重点人才项目(ZDRCA2016082); 江苏省自然科学基金(BK20161433)

Recent advances in non-canonical pyroptosis during sepsis

Fei Peng1, Wei Chang1, Yi Yang1,()   

  1. 1. Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China
  • Received:2017-11-30 Published:2019-02-28
  • Corresponding author: Yi Yang
  • About author:
    Corresponding author: Yang Yi, Email:
引用本文:

彭菲, 常炜, 杨毅. 非经典途径细胞焦亡在脓毒症中的研究进展[J]. 中华重症医学电子杂志, 2019, 05(01): 46-50.

Fei Peng, Wei Chang, Yi Yang. Recent advances in non-canonical pyroptosis during sepsis[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2019, 05(01): 46-50.

脓毒症是宿主对感染产生的失控反应,并出现危及生命的器官功能障碍。细胞焦亡(pyroptosis)是一种以促炎性为特点,依赖于Caspase酶活性的细胞程序性死亡。根据发生机制,将细胞焦亡分为经典焦亡途径和非经典焦亡途径。胞内脂多糖通过结合并激活Caspase-11/4/5,进而剪切并激活Gasdermin D蛋白,分离出活性GSDMD-N端,在胞膜形成gasdermin孔道,诱导细胞焦亡,称之为非经典途径细胞焦亡。细胞焦亡是一把双刃剑,一方面可以抵御病原体感染,另一方面能够导致邻近细胞和组织炎症反应,导致机体全身炎症反应。扩展对细胞焦亡分子机制及作用的认识有助于探索脓毒症治疗的新靶点。

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Pyroptosis is a kind of programmed cell death which characterized as proinflammatory and dependents on the caspase enzyme activity. Its development is mediated by canonical or non-canonical pathways according to the molecular mechanism. Caspase-11/4/5 is activated via combining to the intracellular lipopolysaccharide, and thus cleaves gasdermin D, thereby releasing its N domain with the pore-formingactivity, which forms a large pore in the membrane that induces non-canonical pyroptosis. Pyroptosis is a double-edged sword, which could contribute to immune defense against pathogen infection on one hand. however, on another hand, it induces inflammation of adjacent cell or organs causing systemic inflammation. Expand our knowledge of pyroptotic molecular mechanism and effect is beneficial to explore new potential targets for sepsis therapy.

1
Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) [J]. JAMA, 2016, 315(8): 801-810.
2
Jorgensen I, Miao EA. Pyroptotic cell death defends against intracellular pathogens [J]. Immunol Rev, 2015, 265(1): 130-142.
3
Jorgensen I, Rayamajhi M, Miao EA. Programmed cell death as a defence against infection [J]. Nat Rev Immunol, 2017, 17(3): 151-164.
4
Cookson BT, Brennan MA. Pro-inflammatory programmed cell death [J]. Trends Microbiol, 2001, 9(3): 113-114.
5
Aglietti RA, Dueber EC. Recent insights into the molecular mechanisms underlying pyroptosis and gasdermin family functions [J]. Trends Immunol, 2017, 38(4): 261-271.
6
Chen X, He WT, Hu L, et al. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis [J]. Cell Res, 2016, 26(9): 1007-1020.
7
He WT, Wan H, Hu L, et al. Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion [J]. Cell Res, 2015, 25(12): 1285-1298.
8
Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death [J]. Nature, 2015, 526(7575): 660-665.
9
Miao EA, Leaf IA, Treuting PM, et al. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria [J].Nat Immunol, 2010, 11(12): 1136-1142.
10
Aziz M, Jacob A, Wang P. Revisiting caspases in sepsis [J]. Cell Death Dis, 2014, 5: e1526.
11
Kayagaki N, Warming S, Lamkanfi M, et al. Non-canonical inflammasome activation targets caspase-11 [J]. Nature, 2011, 479(7371): 117-121.
12
Kayagaki N, Stowe IB, Lee BL, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling [J]. Nature, 2015, 526(7575): 666-671.
13
Hagar JA, Powell DA, Aachoui Y, et al. Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock [J]. Science, 2013, 341(6151): 1250-1253.
14
Shi J, Zhao Y, Wang Y, et al. Inflammatory caspases are innate immune receptors for intracellular LPS [J]. Nature, 2014, 514(7521): 187-192.
15
Meunier E, Dick MS, Dreier RF, et al. Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases [J]. Nature, 2014, 509(7500): 366-370.
16
Kayagaki N, Wong MT, Stowe IB, et al. Noncanonical inflammasome activation by intracellular LPS independent of TLR4 [J]. Science, 2013, 341(6151): 1246-1249.
17
Saeki N, Kuwahara Y, Sasaki H, et al. Gasdermin (Gsdm) localizing to mouse Chromosome 11 is predominantly expressed in upper gastrointestinal tract but significantly suppressed in human gastric cancer cells [J]. Mamm Genome, 2000, 11(9): 718-724.
18
Liu X, Zhang Z, Ruan J, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores [J]. Nature, 2016, 535(7610): 153-158.
19
Yang D, He Y, Munoz-Planillo R, et al. Caspase-11 Requires the Pannexin-1 Channel and the Purinergic P2X7 Pore to Mediate Pyroptosis and Endotoxic Shock [J]. Immunity, 2015, 43(5): 923-932.
20
Kovacs SB, Miao EA. Gasdermins: Effectors of pyroptosis [J]. Trends Cell Biol, 2017, 27(9): 673-684.
21
Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family [J]. Nature, 2016, 535(7610): 111-116.
22
Sborgi L, Ruhl S, Mulvihill E, et al. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death [J]. EMBO J, 2016, 35(16): 1766-1778.
23
Shi J, Gao W, Shao F. Pyroptosis: gasdermin-mediated programmed necrotic cell death [J]. Trends Biochem Sci, 2017, 42(4): 245-254.
24
Lamkanfi M, Dixit VM. Manipulation of host cell death pathways during microbial infections [J]. Cell Host Microbe, 2010, 8(1): 44-54.
25
Casson CN, Yu J, Reyes VM, et al. Human caspase-4 mediates noncanonical inflammasome activation against gram-negative bacterial pathogens [J]. Proc Natl Acad Sci U S A, 2015, 112(21): 6688-6693.
26
Akhter A, Caution K, Abu Khweek A, et al. Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with lysosomes by modulating actin polymerization [J]. Immunity, 2012, 37(1): 35-47.
27
Thurston TL, Matthews SA, Jennings E, et al. Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death [J]. Nat Commun, 2016, 7: 13292.
28
Knodler LA, Crowley SM, Sham HP, et al. Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens [J]. Cell Host Microbe, 2014, 16(2): 249-256.
29
Aachoui Y, Leaf IA, Hagar JA, , et al. Caspase-11 protects against bacteria that escape the vacuole [J]. Science, 2013, 339(6122): 975-978.
30
Kuang S, Zheng J, Yang H, et al. Structure insight of GSDMD reveals the basis of GSDMD autoinhibition in cell pyroptosis [J]. Proc Natl Acad Sci U S A, 2017, 114(40): 10642-10647.
31
Man SM, Karki R, Kanneganti TD. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases [J]. Immunol Rev, 2017, 277(1): 61-75.
32
Cheng KT, Xiong S, Ye Z, et al. Caspase-11-mediated endothelial pyroptosis underlies endotoxemia-induced lung injury [J]. J Clin Invest, 2017, 127(11): 4124-4135.
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