Inflammasome-Dependent Peroxiredoxin 2 Secretion Induces the Classical Complement Pathway Activation
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초록
Peroxiredoxins (Prxs) are ubiquitously expressed peroxidases that reduce hydrogen peroxide or alkyl peroxide production in cells. Prxs are released from cells in response to various stress conditions, and they function as damage-associated molecular pattern molecules. However, the secretory mechanism of Prxs and their roles have not been elucidated. Thus, we aimed to determine whether inflammasome activation is a secretory mechanism of Prxs and subsequently identify the effect of the secreted Prxs on activation of the classical complement pathway. Using J774A.1, a murine macrophage cell line, we demonstrated that NLRP3 inflammasome activation induces Prx1, Prx2, Prx5, and Prx6 secretion in a caspase-1 dependent manner. Using HEK293T cells with a transfection system, we revealed that the release of Prx1 and Prx2 relies on gasdermin-D (GSDMD)-mediated secretion. Next, we confirmed the binding of both Prx1 and Prx2 to C1q; however, only Prx2 could induce the C1q-mediated classical complement pathway activation. Collectively, our results suggest that inflammasome activation is a secretory mechanism of Prxs and that GSDMD is a mediator of their secretion. Moreover, secreted Prx1 and Prx2 bind with C1q, but only Prx2 mediates the classical complement pathway activation.
Abstract
Peroxiredoxins (Prxs) are ubiquitously expressed peroxidases that reduce hydrogen peroxide or alkyl peroxide production in cells. Prxs are released from cells in response to various stress conditions, and they function as damage-associated molecular pattern molecules. However, the secretory mechanism of Prxs and their roles have not been elucidated. Thus, we aimed to determine whether inflammasome activation is a secretory mechanism of Prxs and subsequently identify the effect of the secreted Prxs on activation of the classical complement pathway. Using J774A.1, a murine macrophage cell line, we demonstrated that NLRP3 inflammasome activation induces Prx1, Prx2, Prx5, and Prx6 secretion in a caspase-1 dependent manner. Using HEK293T cells with a transfection system, we revealed that the release of Prx1 and Prx2 relies on gasdermin-D (GSDMD)-mediated secretion. Next, we confirmed the binding of both Prx1 and Prx2 to C1q; however, only Prx2 could induce the C1q-mediated classical complement pathway activation. Collectively, our results suggest that inflammasome activation is a secretory mechanism of Prxs and that GSDMD is a mediator of their secretion. Moreover, secreted Prx1 and Prx2 bind with C1q, but only Prx2 mediates the classical complement pathway activation.
참고문헌 (41)
- Cox AG, "Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling", Biochem J, 425, pp.313~325 (2009)
- 이세나, "Peroxiredoxin-3 Is Involved in Bactericidal Activity through the Regulation of Mitochondrial Reactive Oxygen Species", Immune Network, 16(6), pp.373~380 (2016), 대한면역학회[DOI]
- Neumann CA, "Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression", Nature, 424, pp.561~565 (2003)
- Lee TH, "Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice", Blood, 101, pp.5033~5038 (2003)
- Perricone C, "Glutathione : a key player in autoimmunity", Autoimmun Rev, 8, pp.697~701 (2009)
- Shichita T, "Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain", Nat Med, 18, pp.911~917 (2012)
- Salzano S, "Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal", Proc Natl Acad Sci U S A, 111, pp.12157~12162 (2014)
- He Y, "Circulating peroxiredoxin-1 is a novel damage-associated molecular pattern and aggravates acute liver injury via promoting inflammation", Free Radic Biol Med, 137, pp.24~36 (2019)
- Schroder K, "The inflammasomes", Cell, 140, pp.821~832 (2010)
- Feng S, "Mechanisms of gasdermin family members in inflammasome signaling and cell death", J Mol Biol, 430, pp.3068~3080 (2018)
- Ding J, "Pore-forming activity and structural autoinhibition of the gasdermin family", Nature, 535, pp.111~116 (2016)
- Liu X, "Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores", Nature, 535, pp.153~158 (2016)
- Walport MJ, "Complement. First of two parts", N Engl J Med, 344, pp.1058~1066 (2001)
- Walport MJ, "Complement. Second of two parts", N Engl J Med, 344, pp.1140~1144 (2001)
- Païdassi H, "C1q binds phosphatidylserine and likely acts as a multiligand-bridging molecule in apoptotic cell recognition", J Immunol, 180, pp.2329~2338 (2008)
- Kang YH, "Target pattern recognition by complement proteins of the classical and alternative pathways", Adv Exp Med Biol, 653, pp.117~128 (2009)
- Kim SY, "High-mobility group box 1-induced complement activation causes sterile inflammation", Front Immunol, 9, pp.705~ (2018)
- Hornung V, "Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization", Nat Immunol, 9, pp.847~856 (2008)
- Kaplan MH, "Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin", J Immunol, 112, pp.2135~2147 (1974)
- Bhakdi S, "Possible protective role for C-reactive protein in atherogenesis : complement activation by modified lipoproteins halts before detrimental terminal sequence", Circulation, 109, pp.1870~1876 (2004)
- Shi J, "Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death", Nature, 526, pp.660~665 (2015)
- Kayagaki N, "Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling", Nature, 526, pp.666~671 (2015)
- He WT, "Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion", Cell Res, 25, pp.1285~1298 (2015)
- Jeong SJ, "Prdx1(peroxiredoxin 1)deficiency reduces cholesterol efflux via impaired macrophage lipophagic flux", Autophagy, 14, pp.120~133 (2018)
- Jeong Se-Jin, "Deficiency of peroxiredoxin 2 exacerbates angiotensin II-induced abdominal aortic aneurysm", Experimental and Molecular Medicine, 52, pp.1~15 (2020), 생화학분자생물학회[DOI]
- Wang Y, "Peroxiredoxin 3 inhibits acetaminophen-induced liver pyroptosis through the regulation of mitochondrial ROS", Front Immunol, 12, pp.652782~ (2021)
- Nabeshima A, "Peroxiredoxin 4 protects against nonalcoholic steatohepatitis and type 2 diabetes in a nongenetic mouse model", Antioxid Redox Signal, 19, pp.1983~1998 (2013)
- Kim MH, "Peroxiredoxin 5 ameliorates obesity-induced nonalcoholic fatty liver disease through the regulation of oxidative stress and AMP-activated protein kinase signaling", Redox Biol, 28, pp.101315~ (2020)
- 노종성, "Damage-Associated Molecular Patterns in Inflammatory Diseases", Immune Network, 18(4), pp.1~14 (2018), 대한면역학회[DOI]
- 김은지, "Zika Virus Impairs Host NLRP3-mediated Inflammasome Activation in an NS3-dependent Manner", Immune Network, 19(6), pp.1~13 (2019), 대한면역학회[DOI]
- Kishore U, "C1q and tumor necrosis factor superfamily : modularity and versatility", Trends Immunol, 25, pp.551~561 (2004)
- Wang Q, "Identification of a central role for complement in osteoarthritis", Nat Med, 17, pp.1674~1679 (2011)
- Bohana-Kashtan O, "Cell signals transduced by complement", Mol Immunol, 41, pp.583~597 (2004)
- Morgan BP, "Complement membrane attack on nucleated cells : resistance, recovery and non-lethal effects", Biochem J, 264, pp.1~14 (1989)
- Stahl RA, "Enhanced glomerular prostaglandin formation in experimental membranous nephropathy", Kidney Int, 31, pp.1126~1131 (1987)
- Hänsch GM, "Effect of the late complement components C5b-9 on human monocytes : release of prostanoids, oxygen radicals and of a factor inducing cell proliferation", Int Arch Allergy Appl Immunol, 82, pp.317~320 (1987)
- Ruparelia N, "Inflammatory processes in cardiovascular disease : a route to targeted therapies", Nat Rev Cardiol, 14, pp.133~144 (2017)
- Wyss-Coray T, "Inflammation in neurodegenerative disease--a double-edged sword", Neuron, 35, pp.419~432 (2002)
- Hotamisligil GS, "Inflammation and metabolic disorders", Nature, 444, pp.860~867 (2006)
- Coussens LM, "Inflammation and cancer", Nature, 420, pp.860~867 (2002)
- Guo H, "Inflammasomes : mechanism of action, role in disease, and therapeutics", Nat Med, 21, pp.677~687 (2015)