The Crystal-induced Activation of NLRP3 Inflammasomes in Atherosclerosis

Overview

Journal Inflamm Regen

Publisher Biomed Central

Date 2017 Dec 21

PMID 29259717

Citations 24

Authors

Tadayoshi Karasawa

Masafumi Takahashi

Affiliations

Soon will be listed here.

Abstract

Atherosclerosis is an inflammatory disease, which is accompanied by the deposition of cholesterol-rich lipids and the infiltration of macrophages. Other well-known features of atherosclerotic lesions include the deposition of cholesterol crystals and calcium phosphate crystals; however, their pathophysiological role remains unclear. Recent studies suggest that cholesterol crystals play a pivotal role in activation of NLRP3 inflammasomes, which regulate caspase-1 activation and the subsequent processing of IL-1β, in atherosclerotic lesions. NLRP3 inflammasomes are essential for the initiation of vascular inflammation during the progression of atherosclerosis. Therefore, the regulatory mechanisms of NLRP3 inflammasomes are regarded as potential targets for atherosclerosis treatment. Here, we review the current knowledge regarding the role of NLRP3 inflammasomes in the progression of atherosclerosis and the prospects for therapeutic approaches targeting NLRP3 inflammasomes.

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References

Song H, Liu B, Huai W, Yu Z, Wang W, Zhao J . The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation by promoting proteasomal degradation of NLRP3. Nat Commun. 2016; 7:13727. PMC: 5155141. DOI: 10.1038/ncomms13727. View

Baroja-Mazo A, Martin-Sanchez F, Gomez A, Martinez C, Amores-Iniesta J, Compan V . The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol. 2014; 15(8):738-48. DOI: 10.1038/ni.2919. View

Zhou R, Yazdi A, Menu P, Tschopp J . A role for mitochondria in NLRP3 inflammasome activation. Nature. 2010; 469(7329):221-5. DOI: 10.1038/nature09663. View

Karasawa T, Kawashima A, Usui F, Kimura H, Shirasuna K, Inoue Y . Oligomerized CARD16 promotes caspase-1 assembly and IL-1β processing. FEBS Open Bio. 2015; 5:348-56. PMC: 4420773. DOI: 10.1016/j.fob.2015.04.011. View

Franchi L, Amer A, Body-Malapel M, Kanneganti T, Ozoren N, Jagirdar R . Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages. Nat Immunol. 2006; 7(6):576-82. DOI: 10.1038/ni1346. View

Lamkanfi M, Dixit V . Mechanisms and functions of inflammasomes. Cell. 2014; 157(5):1013-22. DOI: 10.1016/j.cell.2014.04.007. View

Razani B, Feng C, Coleman T, Emanuel R, Wen H, Hwang S . Autophagy links inflammasomes to atherosclerotic progression. Cell Metab. 2012; 15(4):534-44. PMC: 3322320. DOI: 10.1016/j.cmet.2012.02.011. View

Gage J, Hasu M, Thabet M, Whitman S . Caspase-1 deficiency decreases atherosclerosis in apolipoprotein E-null mice. Can J Cardiol. 2012; 28(2):222-9. DOI: 10.1016/j.cjca.2011.10.013. View

C Levin T, Wickliffe K, Leppla S, Moayeri M . Heat shock inhibits caspase-1 activity while also preventing its inflammasome-mediated activation by anthrax lethal toxin. Cell Microbiol. 2008; 10(12):2434-46. PMC: 2592509. DOI: 10.1111/j.1462-5822.2008.01220.x. View

10.

Emanuel R, Sergin I, Bhattacharya S, Turner J, Epelman S, Settembre C . Induction of lysosomal biogenesis in atherosclerotic macrophages can rescue lipid-induced lysosomal dysfunction and downstream sequelae. Arterioscler Thromb Vasc Biol. 2014; 34(9):1942-1952. PMC: 4140993. DOI: 10.1161/ATVBAHA.114.303342. View

11.

Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F, Morimoto H . Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. Circulation. 2011; 123(6):594-604. DOI: 10.1161/CIRCULATIONAHA.110.982777. View

12.

Black R, Kronheim S, Merriam J, March C, Hopp T . A pre-aspartate-specific protease from human leukocytes that cleaves pro-interleukin-1 beta. J Biol Chem. 1989; 264(10):5323-6. View

13.

Schmid-Burgk J, Chauhan D, Schmidt T, Ebert T, Reinhardt J, Endl E . A Genome-wide CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) Screen Identifies NEK7 as an Essential Component of NLRP3 Inflammasome Activation. J Biol Chem. 2015; 291(1):103-9. PMC: 4697147. DOI: 10.1074/jbc.C115.700492. View

14.

Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith B, Rajendiran T, Nunez G . K⁺ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity. 2013; 38(6):1142-53. PMC: 3730833. DOI: 10.1016/j.immuni.2013.05.016. View

15.

Juliana C, Fernandes-Alnemri T, Kang S, Farias A, Qin F, Alnemri E . Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation. J Biol Chem. 2012; 287(43):36617-22. PMC: 3476327. DOI: 10.1074/jbc.M112.407130. View

16.

Chong-Shan Shi , Shenderov K, Huang N, Kabat J, Abu-Asab M, Fitzgerald K . Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol. 2012; 13(3):255-63. PMC: 4116819. DOI: 10.1038/ni.2215. View

17.

Guo C, Xie S, Chi Z, Zhang J, Liu Y, Zhang L . Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome. Immunity. 2016; 45(4):802-816. DOI: 10.1016/j.immuni.2016.09.008. View

18.

Komada T, Usui F, Shirasuna K, Kawashima A, Kimura H, Karasawa T . ASC in renal collecting duct epithelial cells contributes to inflammation and injury after unilateral ureteral obstruction. Am J Pathol. 2014; 184(5):1287-98. DOI: 10.1016/j.ajpath.2014.01.014. View

19.

Usui F, Shirasuna K, Kimura H, Tatsumi K, Kawashima A, Karasawa T . Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice. Biochem Biophys Res Commun. 2012; 425(2):162-8. DOI: 10.1016/j.bbrc.2012.07.058. View

20.

Stehlik C, Dorfleutner A . COPs and POPs: modulators of inflammasome activity. J Immunol. 2007; 179(12):7993-8. PMC: 2645488. DOI: 10.4049/jimmunol.179.12.7993. View