Citations to this article
Citation Information: JCI Insight. 2018;3(13):e99692. https://doi.org/10.1172/jci.insight.99692.
Abstract
BACKGROUND. Necroptosis is a form of programmed necrotic cell death that is rapidly emerging as an important pathophysiological pathway in numerous disease states. Necroptosis is dependent on receptor-interacting protein kinase 3 (RIPK3), a protein shown to play an important role in experimental models of critical illness. However, there is limited clinical evidence regarding the role of extracellular RIPK3 in human critical illness. METHODS. Plasma RIPK3 levels were measured in 953 patients prospectively enrolled in 5 ongoing intensive care unit (ICU) cohorts in both the USA and Korea. RIPK3 concentrations among groups were compared using prospectively collected phenotypic and outcomes data. RESULTS. In all 5 cohorts, extracellular RIPK3 levels in the plasma were higher in patients who died in the hospital compared with those who survived to discharge. In a combined analysis, increasing RIPK3 levels were associated with elevated odds of in-hospital mortality (odds ratio [OR] 1.7 for each log10-unit increase in RIPK3 level, P < 0.0001). When adjusted for baseline severity of illness, the OR for in-hospital mortality remained statistically significant (OR 1.33, P = 0.007). Higher RIPK3 levels were also associated with more severe organ failure. CONCLUSIONS. Our findings suggest that elevated levels of RIPK3 in the plasma of patients admitted to the ICU are associated with in-hospital mortality and organ failure. FUNDING. Supported by NIH grants P01 HL108801, R01 HL079904, R01 HL055330, R01 HL060234, K99 HL125899, and KL2TR000458-10. Supported by Samsung Medical Center grant SMX1161431.
Authors
Kevin C. Ma, Edward J. Schenck, Ilias I. Siempos, Suzanne M. Cloonan, Eli J. Finkelsztein, Maria A. Pabon, Clara Oromendia, Karla V. Ballman, Rebecca M. Baron, Laura E. Fredenburgh, Angelica Higuera, Jin Young Lee, Chi Ryang Chung, Kyeongman Jeon, Jeong Hoon Yang, Judie A. Howrylak, Jin-Won Huh, Gee Young Suh, Augustine M.K. Choi
Citations to this article (30)
| Title and authors | Publication | Year |
|---|---|---|
|
Mediators of necroptosis: from cell death to metabolic regulation.
Wu X, Nagy LE, Gautheron J |
EMBO Molecular Medicine | 2024 |
|
The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism.
Lu X, Li G, Liu Y, Luo G, Ding S, Zhang T, Li N, Geng Q |
Cellular and molecular life sciences : CMLS | 2024 |
|
Acute lung injury: a view from the perspective of necroptosis.
Dong J, Liu W, Liu W, Wen Y, Liu Q, Wang H, Xiang G, Liu Y, Hao H |
Inflammation research : official journal of the European Histamine Research Society ... [et al.] | 2024 |
|
Circulating Markers of Necroptosis in Acute Pancreatitis.
Belfrage H, Kuuliala K, Kuuliala A, Mustonen H, Puolakkainen P, Kylänpää L, Louhimo J |
Digestive diseases and sciences | 2024 |
|
Highly secreted tryptophanyl tRNA synthetase 1 as a potential theranostic target for hypercytokinemic severe sepsis.
Kim YT, Huh JW, Choi YH, Yoon HK, Nguyen TT, Chun E, Jeong G, Park S, Ahn S, Lee WK, Noh YW, Lee KS, Ahn HS, Lee C, Lee SM, Kim KS, Suh GJ, Jeon K, Kim S, Jin M |
EMBO Molecular Medicine | 2023 |
|
Angiopoietin 2 is associated with vascular necroptosis induction in COVID-19 acute respiratory distress syndrome
D Price, E Benedetti, K Hoffman, L Gomez-Escobar, S Alvarez-Mulett, A Capili, H Sarwath, C Parkhurst, E Lafond, K Weidman, A Ravishankar, J Cheong, R Batra, M Büyüközkan, K Chetnik, I Easthausen, E Schenck, A Racanelli, H Reed, J Laurence, S Josefowicz, L Lief, M Choi, F Schmidt, A Borczuk, A Choi, J Krumsiek, S Rafii |
The American Journal of Pathology | 2022 |
|
Interferon-γ Preferentially Promotes Necroptosis of Lung Epithelial Cells by Upregulating MLKL
Q Hao, S Shetty, T Tucker, S Idell, H Tang |
Cells | 2022 |
|
Sepsis subphenotyping based on organ dysfunction trajectory
Xu Z, Mao C, Su C, Zhang H, Siempos I, Torres LK, Pan D, Luo Y, Schenck EJ, Wang F |
Critical Care | 2022 |
|
Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis.
Choi H, Yoo H, Lee JY, Park J, Jeon K |
Biomedicines | 2022 |
|
Differential role of MLKL in alcohol-associated and non-alcoholic fatty liver disease in mice and human
Tatsunori Miyata, Xiaoqin Wu, Xiude Fan, Emily Huang, Carlos Sanz-Garcia, Christina K. Cajigas-Du Ross, Sanjoy Roychowdhury, Annette Bellar, Megan R. McMullen, Jaividhya Dasarathy, Daniela Allende, Joan Caballeria, Pau Sancho-Bru, Craig J. McClain, Mack C. Mitchell, Arthur J. McCullough, Svetlana Radaeva, Bruce A. Barton, Gyongyi Szabo, Srinivasan Dasarathy, Laura E Nagy |
JCI Insight | 2021 |
|
Necroptosis, pyroptosis and apoptosis: an intricate game of cell death
D Bertheloot, E Latz, BS Franklin |
Cellular and Molecular Immunology | 2021 |
|
Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes
H Yoo, Y Im, RE Ko, JY Lee, J Park, K Jeon |
Scientific Reports | 2021 |
|
The Elk1/MMP-9 axis regulates E-cadherin and occludin in ventilator-induced lung injury
Z Tao, Y Jie, Z Mingru, G Changping, Y Fan, W Haifeng, W Yuelan |
Respiratory Research | 2021 |
|
The potential value of plasma receptor interacting protein 3 in neonates with culture-positive late-onset sepsis
C Gao, Z Feng, L Wang, X Zhao, K Fu, S Ma, Z Yang, S Wang, S Yu |
BMC Infectious Diseases | 2021 |
|
Exosomal CD63 in critically ill patients with sepsis
Y Im, H Yoo, RE Ko, JY Lee, J Park, K Jeon |
Scientific Reports | 2021 |
|
M1 Macrophages Are More Susceptible to Necroptosis.
Hao Q, Idell S, Tang H |
Journal of cellular immunology | 2021 |
|
Association of plasma exosomes with severity of organ failure and mortality in patients with sepsis
Y Im, H Yoo, JY Lee, J Park, GY Suh, K Jeon |
Journal of Cellular and Molecular Medicine | 2020 |
|
Decreased IDO1-dependent tryptophan metabolism in aged lung during influenza
SJ Cho, KS Hong, E Schenck, S Lee, R Harris, J Yang, AM Choi, H Stout-Delgado |
The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology | 2020 |
|
The pathophysiology of SARS-CoV-2: A suggested model and therapeutic approach
G Morris, CC Bortolasci, BK Puri, L Olive, W Marx, A O'Neil, E Athan, A Carvalho, M Maes, K Walder, M Berk |
Life Sciences | 2020 |
|
Association of Plasma Level of TNF-Related Apoptosis-Inducing Ligand with Severity and Outcome of Sepsis
H Yoo, JY Lee, J Park, JH Yang, GY Suh, K Jeon |
Journal of Clinical Medicine | 2020 |
|
Propofol-induced MiR-20b expression initiates endogenous cellular signal changes mitigating hypoxia/re-oxygenation-induced endothelial autophagy in vitro
Y Lu, S Wang, S Cai, X Gu, J Wang, Y Yang, Z Hu, X Zhang, Y Ye, S Shen, K Joshi, D Ma, L Zhang |
Cell Death and Disease | 2020 |
|
Collateral damage: necroptosis in the development of lung injury
H Faust, NS Mangalmurti |
American journal of physiology. Lung cellular and molecular physiology | 2020 |
|
Circulating Receptor-Interacting Protein Kinase 3 Are Increased in HBV Patients With Acute-on-Chronic Liver Failure and Are Associated With Clinical Outcome
L Chen, Z Cao, L Yan, Y Ding, X Shen, K Liu, X Xiang, Q Xie, C Zhu, S Bao, H Wang |
Frontiers in physiology | 2020 |
|
Role of Damage-Associated Molecular Patterns in Light of Modern Environmental Research: A Tautological Approach
WG Land |
INT J ENVIRON RES | 2020 |
|
mtDNA-STING pathway promotes necroptosis-dependent enterocyte injury in intestinal ischemia reperfusion
X Zhang, J Wu, Q Liu, X Li, S Li, J Chen, Z Hong, X Wu, Y Zhao, J Ren |
Cell Death and Disease | 2020 |
|
Circulating cell death biomarker TRAIL is associated with increased organ dysfunction in sepsis
Edward Schenck, Kevin Ma, David R Price, Thomas Nicholson, Clara Oromendia, Eliza R Gentzler, elizabeth sanchez, Rebecca Baron, Laura Fredenburgh, Jin Won Huh, Ilias I. Siempos, Augustine Choi |
JCI Insight | 2019 |
|
Integrating molecular pathogenesis and clinical translation in sepsis-induced acute respiratory distress syndrome
Joshua Englert, Christopher Bobba, Rebecca Baron |
JCI Insight | 2019 |
|
Necroptosis: a crucial pathogenic mediator of human disease
Mary Choi, David R Price, Stefan W. Ryter, Augustine Choi |
JCI Insight | 2019 |
|
Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study
MG Shashaty, JP Reilly, HE Faust, CM Forker, CA Ittner, PX Zhang, MJ Hotz, D Fitzgerald, W Yang, BJ Anderson, DN Holena, PN Lanken, JD Christie, NJ Meyer, NS Mangalmurti |
Critical Care | 2019 |
|
A Phase I Trial of Low Dose Inhaled Carbon Monoxide in Sepsis-Induced ARDS
Laura Fredenburgh, Mark Perrella, Diana Barragan-Bradford, Dean Hess, Elizabeth Peters, Karen Welty-Wolf, Bryan Kraft, R. Scott Harris, Rie Maurer, Kiichi Nakahira, Clara Oromendia, John Davies, Angelica Higuera, Kristen Schiffer, Joshua Englert, Paul Dieffenbach, David Berlin, Susan Lagambina, Mark Bouthot, Andrew Sullivan, Paul Nuccio, Mamary Kone, Mona Malik, Maria Angelica Pabon Porras, Eli J Finkelsztein, Tilo Winkler, Shelley Hurwitz, Charles N. Serhan, Claude A Piantadosi, Rebecca Baron, B. Taylor Thompson, Augustine Choi |
JCI Insight | 2018 |
