The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease

ZHANG Wenjie; SUN Diyang; WANG Pei

doi:10.3969/j.issn.1006-0111.201902051

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Volume 38 Issue 1

Mar. 2020

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2020 > 38(1): 9-13,41

ZHANG Wenjie, SUN Diyang, WANG Pei. The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(1): 9-13,41. doi: 10.3969/j.issn.1006-0111.201902051

Citation:

ZHANG Wenjie, SUN Diyang, WANG Pei. The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(1): 9-13,41. doi: 10.3969/j.issn.1006-0111.201902051

The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease

doi: 10.3969/j.issn.1006-0111.201902051

Department of Pharmacology, School of Pharmacy, Naval Medical University, Shanghai, 200433 China

Received Date: 2019-02-22
Rev Recd Date: 2019-07-18

Abstract

Non-alcoholic fatty liver disease (NAFLD), which is a series of diseases including simple fatty liver, nonalcoholic steatohepatitis and cirrhosis, is one of the main causes of liver cirrhosis, carcinoma and liver transplantation. The mechanism of NAFLD is not fully understood. Besides the physical exercise and diet intervention, there is no recognized effective drug therapy for NAFLD. Pyroptosis is a newly discovered type of programmed cell death, which is associated with activation of caspase-1, or caspase-2 mediated inflammasome activation. The main function of inflammasome is to activate caspase-1, which indirectly regulates the expression and secretion of inflammatory factors interleukin-1 and interleukin-18. Recent studies have shown that inflammasome-associated pyroptosis plays a key role in NAFLD. This review will discuss the latest researches in this field to provide new scientific knowledge for prevention and treatment of NAFLD.
- inflammasome,
- pyroptosis,
- non-alcoholic fatty liver disease,
- drug target,
- caspase-1

References

[1]	VILLANUEVA M T. Conscious uncoupling in NASH[J]. Nat Rev Drug Discov,2017,16(4):239
[2]	NEUSCHWANDER-TETRI B A. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites[J]. Hepatology,2010,52(2):774-788
[3]	MARRA F, SVEGLIATI-BARONI G. Lipotoxicity and the gut-liver axis in NASH pathogenesis[J]. J Hepatol,2018,68(2):280-295
[4]	PEVERILL W, POWELL L, SKOIEN R. Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation[J]. Int J Mol Sci,2014,15(5):8591-8638
[5]	LAZIC M, INZAUGARAT M E, POVERO D, et al. Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis[J]. Plos One,2014,9(9):e107658
[6]	ABDELMALEK M F, SUZUKI A, GUY C, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease[J]. Hepatology,2010,51(6):1961-1971
[7]	IOANNOU G N, VAN ROOYEN D M, SAVARD C, et al. Cholesterol-lowering drugs cause dissolution of cholesterol crystals and disperse Kupffer cell crown-like structures during resolution of NASH[J]. J Lipid Res,2015,56(2):277-285
[8]	MIELE L C, MARRONE G, LAURITANO C, et al. Gut-liver axis and microbiota in NAFLD: insight pathophysiology for novel therapeutic target[J]. Curr Pharm Des,2013,19(29):5314-5324
[9]	SCHRODER K, TSCHOPP J. The inflammasomes[J]. Cell,2010,140(6):821-832
[10]	MINKIEWICZ J, DE RIVERO VACCARI J P, KEANE R W. Human astrocytes express a novel NLRP2 inflammasome[J]. Glia,2013,61(7):1113-1121
[11]	Wlodarska M, Thaiss CA, Nowarski R, et al. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion[J]. Cell,2014,156(5):1045-1059
[12]	OHASHI K, WANG Z J, YANG Y M, et al. NOD-like receptor C4 inflammasome regulates the growth of colon cancer liver metastasis in NAFLD[J]. Hepatology,2019:30693
[13]	DING J J, WANG K, LIU W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family[J]. Nature,2016,535(7610):111-116
[14]	WREE A, MCGEOUGH M D, PEÑA C A, et al. NLRP3 inflammasome activation is required for fibrosis development in NAFLD[J]. J Mol Med,2014,92(10):1069-1082
[15]	MATSUZAKA T, ATSUMI A, MATSUMORI R, et al. Elovl6 promotes nonalcoholic steatohepatitis[J]. Hepatology,2012,56(6):2199-2208
[16]	WEN H T, GRIS D, LEI Y, et al. Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling[J]. Nat Immunol,2011,12(5):408-415
[17]	WREE A, EGUCHI A, MCGEOUGH M D, et al. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice[J]. Hepatology,2014,59(3):898-910
[18]	MRIDHA A R, WREE A, ROBERTSON A A B, et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice[J]. J Hepatol,2017,66(5):1037-1046
[19]	YANG S J, LIM Y. Resveratrol ameliorates hepatic metaflammation and inhibits NLRP3 inflammasome activation[J]. Metabolism,2014,63(5):693-701
[20]	XU B, JIANG M, CHU Y, et al. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice[J]. J Hepatol,2018,68(4):773-782
[21]	MIURA K, KODAMA Y, INOKUCHI S, et al. Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1β in mice[J]. Gastroenterology,2010,139(1):323-334.e7
[22]	STIENSTRA R, SAUDALE F, DUVAL C, et al. Kupffer cells promote hepatic steatosis via interleukin-1β-dependent suppression of peroxisome proliferator-activated receptor α activity[J]. Hepatology,2010,51(2):511-522
[23]	VANDANMAGSAR B, YOUM Y, RAVUSSIN A, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance[J]. Nat Med,2011,17(2):179-188
[24]	PETRASEK J, BALA S S, CSAK T, et al. IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice[J]. J Clin Invest,2012,122(10):3476-3489
[25]	WITEK R P, STONE W C, KARACA F G, et al. Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis[J]. Hepatology,2009,50(5):1421-1430
[26]	KIM S H, KIM G, HAN D H, et al. Ezetimibe ameliorates steatohepatitis via AMP activated protein kinase-TFEB-mediated activation of autophagy and NLRP3 inflammasome inhibition[J]. Autophagy,2017,13(10):1767-1781
[27]	HENAO-MEJIA J, ELINAV E, JIN C C, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity[J]. Nature,2012,482(7384):179-185
[28]	DE MINICIS S, RYCHLICKI C, AGOSTINELLI L, et al. Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice[J]. Hepatology,2014,59(5):1738-1749
[29]	CSAK T, PILLAI A, GANZ M, et al. Both bone marrow-derived and non-bone marrow-derived cells contribute to AIM2 and NLRP3 inflammasome activation in a MyD88-dependent manner in dietary steatohepatitis[J]. Liver Int,2014,34(9):1402-1413
[30]	MURPHY A J, KRAAKMAN M J, KAMMOUN H L, et al. IL-18 production from the NLRP1 inflammasome prevents obesity and metabolic syndrome[J]. Cell Metab,2016,23(1):155-164
[31]	ANITHA M, REICHARDT F, TABATABAVAKILI S, et al. Intestinal dysbiosis contributes to the delayed gastrointestinal transit in high-fat diet fed mice[J]. Cell Mol Gastroenterol Hepatol,2016,2(3):328-339
[32]	CHEN G Y, LIU M C, WANG F Y, et al. A functional role for Nlrp6 in intestinal inflammation and tumorigenesis[J]. J Immunol,2011,186(12):7187-7194
[33]	ZHANG Q, RAOOF M, CHEN Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury[J]. Nature,2010,464(7285):104-107
[34]	SUN Q, LOUGHRAN P, SHAPIRO R, et al. Redox-dependent regulation of hepatocyte absent in melanoma 2 inflammasome activation in sterile liver injury in mice[J]. Hepatology,2017,65(1):253-268
[35]	WATANABE A, SOHAIL M A, GOMES D A, et al. Inflammasome-mediated regulation of hepatic stellate cells[J]. Am J Physiol Gastrointest Liver Physiol,2009,296(6):G1248-G1257
[36]	WREE A, MCGEOUGH M D, INZAUGARAT M E, et al. NLRP3 inflammasome driven liver injury and fibrosis: Roles of IL-17 and TNF in mice[J]. Hepatology,2018,67(2):736-749

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The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease

Department of Pharmacology, School of Pharmacy, Naval Medical University, Shanghai, 200433 China

Received Date: 2019-02-22

Rev Recd Date: 2019-07-18

Key words:

Abstract: Non-alcoholic fatty liver disease (NAFLD), which is a series of diseases including simple fatty liver, nonalcoholic steatohepatitis and cirrhosis, is one of the main causes of liver cirrhosis, carcinoma and liver transplantation. The mechanism of NAFLD is not fully understood. Besides the physical exercise and diet intervention, there is no recognized effective drug therapy for NAFLD. Pyroptosis is a newly discovered type of programmed cell death, which is associated with activation of caspase-1, or caspase-2 mediated inflammasome activation. The main function of inflammasome is to activate caspase-1, which indirectly regulates the expression and secretion of inflammatory factors interleukin-1 and interleukin-18. Recent studies have shown that inflammasome-associated pyroptosis plays a key role in NAFLD. This review will discuss the latest researches in this field to provide new scientific knowledge for prevention and treatment of NAFLD.

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Reference (36)

[1]	VILLANUEVA M T. Conscious uncoupling in NASH[J]. Nat Rev Drug Discov,2017,16(4):239
[2]	NEUSCHWANDER-TETRI B A. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites[J]. Hepatology,2010,52(2):774-788
[3]	MARRA F, SVEGLIATI-BARONI G. Lipotoxicity and the gut-liver axis in NASH pathogenesis[J]. J Hepatol,2018,68(2):280-295
[4]	PEVERILL W, POWELL L, SKOIEN R. Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation[J]. Int J Mol Sci,2014,15(5):8591-8638
[5]	LAZIC M, INZAUGARAT M E, POVERO D, et al. Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis[J]. Plos One,2014,9(9):e107658
[6]	ABDELMALEK M F, SUZUKI A, GUY C, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease[J]. Hepatology,2010,51(6):1961-1971
[7]	IOANNOU G N, VAN ROOYEN D M, SAVARD C, et al. Cholesterol-lowering drugs cause dissolution of cholesterol crystals and disperse Kupffer cell crown-like structures during resolution of NASH[J]. J Lipid Res,2015,56(2):277-285
[8]	MIELE L C, MARRONE G, LAURITANO C, et al. Gut-liver axis and microbiota in NAFLD: insight pathophysiology for novel therapeutic target[J]. Curr Pharm Des,2013,19(29):5314-5324
[9]	SCHRODER K, TSCHOPP J. The inflammasomes[J]. Cell,2010,140(6):821-832
[10]	MINKIEWICZ J, DE RIVERO VACCARI J P, KEANE R W. Human astrocytes express a novel NLRP2 inflammasome[J]. Glia,2013,61(7):1113-1121
[11]	Wlodarska M, Thaiss CA, Nowarski R, et al. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion[J]. Cell,2014,156(5):1045-1059
[12]	OHASHI K, WANG Z J, YANG Y M, et al. NOD-like receptor C4 inflammasome regulates the growth of colon cancer liver metastasis in NAFLD[J]. Hepatology,2019:30693
[13]	DING J J, WANG K, LIU W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family[J]. Nature,2016,535(7610):111-116
[14]	WREE A, MCGEOUGH M D, PEÑA C A, et al. NLRP3 inflammasome activation is required for fibrosis development in NAFLD[J]. J Mol Med,2014,92(10):1069-1082
[15]	MATSUZAKA T, ATSUMI A, MATSUMORI R, et al. Elovl6 promotes nonalcoholic steatohepatitis[J]. Hepatology,2012,56(6):2199-2208
[16]	WEN H T, GRIS D, LEI Y, et al. Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling[J]. Nat Immunol,2011,12(5):408-415
[17]	WREE A, EGUCHI A, MCGEOUGH M D, et al. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice[J]. Hepatology,2014,59(3):898-910
[18]	MRIDHA A R, WREE A, ROBERTSON A A B, et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice[J]. J Hepatol,2017,66(5):1037-1046
[19]	YANG S J, LIM Y. Resveratrol ameliorates hepatic metaflammation and inhibits NLRP3 inflammasome activation[J]. Metabolism,2014,63(5):693-701
[20]	XU B, JIANG M, CHU Y, et al. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice[J]. J Hepatol,2018,68(4):773-782
[21]	MIURA K, KODAMA Y, INOKUCHI S, et al. Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1β in mice[J]. Gastroenterology,2010,139(1):323-334.e7
[22]	STIENSTRA R, SAUDALE F, DUVAL C, et al. Kupffer cells promote hepatic steatosis via interleukin-1β-dependent suppression of peroxisome proliferator-activated receptor α activity[J]. Hepatology,2010,51(2):511-522
[23]	VANDANMAGSAR B, YOUM Y, RAVUSSIN A, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance[J]. Nat Med,2011,17(2):179-188
[24]	PETRASEK J, BALA S S, CSAK T, et al. IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice[J]. J Clin Invest,2012,122(10):3476-3489
[25]	WITEK R P, STONE W C, KARACA F G, et al. Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis[J]. Hepatology,2009,50(5):1421-1430
[26]	KIM S H, KIM G, HAN D H, et al. Ezetimibe ameliorates steatohepatitis via AMP activated protein kinase-TFEB-mediated activation of autophagy and NLRP3 inflammasome inhibition[J]. Autophagy,2017,13(10):1767-1781
[27]	HENAO-MEJIA J, ELINAV E, JIN C C, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity[J]. Nature,2012,482(7384):179-185
[28]	DE MINICIS S, RYCHLICKI C, AGOSTINELLI L, et al. Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice[J]. Hepatology,2014,59(5):1738-1749
[29]	CSAK T, PILLAI A, GANZ M, et al. Both bone marrow-derived and non-bone marrow-derived cells contribute to AIM2 and NLRP3 inflammasome activation in a MyD88-dependent manner in dietary steatohepatitis[J]. Liver Int,2014,34(9):1402-1413
[30]	MURPHY A J, KRAAKMAN M J, KAMMOUN H L, et al. IL-18 production from the NLRP1 inflammasome prevents obesity and metabolic syndrome[J]. Cell Metab,2016,23(1):155-164
[31]	ANITHA M, REICHARDT F, TABATABAVAKILI S, et al. Intestinal dysbiosis contributes to the delayed gastrointestinal transit in high-fat diet fed mice[J]. Cell Mol Gastroenterol Hepatol,2016,2(3):328-339
[32]	CHEN G Y, LIU M C, WANG F Y, et al. A functional role for Nlrp6 in intestinal inflammation and tumorigenesis[J]. J Immunol,2011,186(12):7187-7194
[33]	ZHANG Q, RAOOF M, CHEN Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury[J]. Nature,2010,464(7285):104-107
[34]	SUN Q, LOUGHRAN P, SHAPIRO R, et al. Redox-dependent regulation of hepatocyte absent in melanoma 2 inflammasome activation in sterile liver injury in mice[J]. Hepatology,2017,65(1):253-268
[35]	WATANABE A, SOHAIL M A, GOMES D A, et al. Inflammasome-mediated regulation of hepatic stellate cells[J]. Am J Physiol Gastrointest Liver Physiol,2009,296(6):G1248-G1257
[36]	WREE A, MCGEOUGH M D, INZAUGARAT M E, et al. NLRP3 inflammasome driven liver injury and fibrosis: Roles of IL-17 and TNF in mice[J]. Hepatology,2018,67(2):736-749

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The role and mechanism of inflammasome-associated pyroptosis in nonalcoholic fatty liver disease

doi: 10.3969/j.issn.1006-0111.201902051

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通讯作者: 陈斌, bchen63@163.com

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