Role of pyroptosis in COVID-19
Mehmet Çelik 1 * ,
Mehmet Reşat Ceylan 1,
Mahmut Alp Karahan 2,
İsmail Koyuncu 3,
Nevin Güler Dinçer 4,
Sevil Alkan 5 More Detail
1 Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, University of Harran, Şanlıurfa, Turkey
2 Department of Anesthesiology, Faculty of Medicine, University of Harran, Şanlıurfa, Turkey
3 Department of Medical Biochemistry, Faculty of Medicine, University of Harran, Şanlıurfa, Turkey
4 Department of Statistics, Faculty of Science, University of Muğla Sıtkı Koçman, Muğla, Turkey
5 Department of Infectious Diseases, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale, Turkey
* Corresponding Author
J CLIN MED KAZ, Volume 20, Issue 2, pp. 39-45.
https://doi.org/10.23950/jcmk/13142
OPEN ACCESS
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ABSTRACT
Aim: In this study, we aimed to investigate the relationship between gasdermin-D, caspase-1, IL-1β and NLRP3, biomarkers that play an important role in COVID-19, and pyroptosis.
Material and Methods: This study was carried out with 58 participants, 28 (48.28%) of whom were diagnosis with COVID-19, and 30 (51.72%) of whom were healthy volunteers (control group).
Results: There were no statistically significant differences between the gasdermin-D, caspase-1, IL-1β, and NLRP3 levels as a result of all statistical comparisons performed. However, IL-1β values both during the discharge period and during the hospitalization period were considerably higher than those of the control group. At the discharge period, IL-1β values of the patients with severe COVID-19 category had higher than moderate patients, and the patients with moderate than the patients with mild patients.
Conclusion: It was observed that IL-1β, which is one of the cytokines released as a result of cell death in the pyroptosis mechanism, was higher in the COVID-19 patients in both the hospitalization and discharge periods compared to the control group. Although not statistically significant these results could support the relationship between pyroptosis and COVID-19.
REFERENCES
- Rabi FA, Zoubi MS, Kasasbeh GA, Salameh DM, Al-Nasser AD. SARS-CoV-2 and coronavirus disease 2019: What we know so far. Pathogens. 2020;9:231. https://doi.org/10.3390/pathogens9030231
- Republic of Turkey Ministry of Health, General Directorate of Public Health. COVID-19 (SARS-CoV-2 infection) general information, epidemiology and diagnosis. https://covid19.saglik.gov.tr/TR-66337/genel-bilgiler-epidemiyoloji-ve-tani.html. [Accessed 10 May 2022].
- WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020: World Health Organization; 2020. Available: https://www. who. int/ dg/ speeches/ detail/ who- director- general- s- openingremarks- at- the- media- briefing- on- covid- 19- 11- march- 2020 [Accessed 9 Apr 2020].
- WHO Coronavirus (COVID-19) Dashboard. Available: https://covid19.who.int/ [Accessed 10 May 2022].
- Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus Infected Pneumonia. N Engl J Med. 2020;382:1199. https://doi:10.1056/NEJMoa2001316
- Pincemail J, Cavalier E, Charlier C, Cheramy-Bien JP, Brevers E, Courtois A, et al. Oxidative Stress Status in COVID-19 Patients Hospitalized in Intensive Care Unit for Severe Pneumonia. A Pilot Study. Antioxidants. 2021;10:257. https://doi.org/10.3390/antiox10020257
- Ardahanlı I, Akhan O, Aslan R, Celik M, Akyüz O. A new index in the follow-up of arrhythmia of Coronavirus Disease-2019 (COVID-19) patients receiving Hydroxychloroquine and Azithromycin therapy; index of cardiac electrophysiological balance. Cumhuriyet Medical Journal. 2021; 43(1):1-7. https://doi.org/10.7197/cmj.870158
- Yıldırım AC, Alkan Cevıker S, Zeren S, Ekıcı MF, Yaylak F, Algın MC, Arık Ö. COVID-19 and related gastrointestinal symptoms: An observational study. Marmara Medical Journal. 2022; 35(2):244-248. https://doi.org/10.5472/marumj.1121879
- Evlice O, Örs Şendoğan D, Ak Ö. Hemodializ Hastalarında COVID-19'un klinik seyri ve mortalite öngördürücüleri, tek merkez deneyimi. Biotech&Strategic Health Res. 2021; 5(2):105-112. https://doi.org/10.34084/bshr.929708
- Dindar Demiray EK, Yılmaz M, Alıravcı ID, Alkan S. COVID-19-Akut Pankreatit İlişkisinin İncelenmesi. İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi. 2021; (13):130-143. https://doi.org/10.38079/igusabder.815768
- Ardahanli I, Akhan O, Sahin E, Akgun O, Gurbanov, R. Myocardial performance index increases at long‐term follow‐up in patients with mild to moderate COVID‐19. Echocardiography. 2022; 39(4):620-625. https://doi.org/10.1111/echo.15340
- Üzümcügil AO, Demirkiran ND, Öner SK, Akkurt A, Alkan Çeviker S. Limb Ischemia Associated With Covid-19 and Its Treatment With Above-Knee Amputation. Int J Low Extrem Wounds. 2022;21(2):197-200. https://doi.org/10.1177/15347346211063257
- Avcı E, Ardahanlı İ, Öztaş E, Dişibeyaz S. Is there a relationship between gastrointestinal symptoms and disease course and prognosis in COVID-19? A single-center pilot study. The Turkish Journal of Academic Gastroenterology. 2020; 19:103-108.
- Alkan Çeviker S, Şener A, Yüksel C, Önder T, Akça A, Vurucu S, et al. Angioedema and acute urticaria in a patient with COVID 19 pneumonia: Favipiravir side effect or COVID-19 cutaneous manifestation. Journal of Emergency Medicine Case Reports. 2021; 12(2):65-67. https://doi.org/10.33706/jemcr.851107
- Li JX, Chen LJ, Zhou CH, Bai F, Zhao Y, Zhang JG, et al. Insight to Proptosis in Viral Infectious Diseases. Health 2021;13:574-590. https://doi.org/10.4236/health.2021.135043
- de Rivero Vaccari JC, Dietrich WD, Keane RW, de Rivero Vaccari JP. The Inflammasome in Times of COVID-19. Front Immunol. 2020; 11:583373. https://doi.org/10.3389/fimmu.2020.583373
- Ferreira AC, Soares VC, de Azevedo-Quintanilha IG, Dias SDSG, Fintelman-Rodrigues N, Sacramento CQ, et al. SARS-CoV-2 engages inflammasome and proptosis in human primary monocytes. Cell Death Discov. 2021; 7(1):1-12. https://doi.org/10.1038/s41420-021-00428-w
- Qian Xu, Yongjian Yang, Xiuren Zhang, James J. Cai. Association of proptosis and severeness of COVID-19 as revealed by integrated single-cell transcriptome data analysis. İmmuno Informatics. 2022; 6:100013. https://doi.org/10.1016/j.immuno.2022.100013
- Republic of Turkey Ministry of Health, General Directorate of Public Health. COVID-19 (SARS-CoV-2 infection) Adult Patient Treatment. covid19.saglik.gov.tr/TR-66926/eriskin-hasta-tedavisi.html [Accessed 10 May 2022].
- Frank D, Vince JE. Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ. 2019; 26(1):99-114. https://doi.org/10.1038/s41418-018-0212-6
- Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972; 26:239–257. https://doi.org/10.1038/bjc.1972.33
- Lindqvist LM, Frank D, McArthur K, Dite TA, Lazarou M, Oakhill JS, et al. Autophagy induced during apoptosis degrades mitochondria and inhibits type I interferon secretion. Cell Death Differ. 2017; 25:782–794. https://doi.org/10.1038/s41418-017-0017-z
- Segawa K, Nagata S. An apoptotic ‘eat me’ signal: phosphatidylserine exposure. Trends Cell Biol. 2015; 25:639–650. https://doi.org/10.1016/j.tcb.2015.08.003
- White MJ, McArthur K, Metcalf D, Lane RM, Cambier JC, Herold MJ, et al. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell. 2014; 159:1549–1562. https://doi.org/10.1016/j.cell.2014.11.036
- Menu P, Vince JE. The NLRP3 inflammasome in health and disease: the good, the bad and the ugly. Clin Exp Immunol. 2011; 166:1–15. https://doi.org/10.1111/j.1365-2249.2011.04440.x
- Broz P, Dixit V. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol. 2016;16:407-420. https://doi.org/10.1038/nri.2016.58
- Yap JK, Moriyama M, Iwasaki A. Inflammasomes and Proptosis as Therapeutic Targets for COVID-19. J Immunol. 2020; 205(2):307-312. https://doi.org/10.4049/jimmunol.2000513
- Chen S, Mei S, Luo Y, Wu H, Zhang J, Zhu J. Gasdermin Family: A Promising Therapeutic Target for Stroke. Transl Stroke Res. 2018; 9:555-563. https://doi.org/10.1007/s12975-018-0666-3
- Jorgensen I, Rayamajhi M, Miao EA. Programmed Cell Death as a Defence against Infection. Nat Rev Immunol. 2017; 17:151-164. https://doi.org/10.1038/nri.2016.147
- Soy M, Keser G, Atagunduz P, Tabak F, Atagunduz I, Kayhan S. Cytokine Storm in COVID-19: Pathogenesis and Overview of Anti-Inflammatory Agents Used in Treatment. Clin Rheumatol. 2020; 39:2085-2094. https://doi.org/10.1007/s10067-020-05190-5
- Freeman TL, Swartz TH. Targeting the NLRP3 Inflammasome in Severe COVID-19. Front Immunol. 2020; 11:1518. https://doi.org/10.3389/fimmu.2020.01518
- Jiang Y, Li J, Teng Y, Sun H, Tian G, He L, et al. Complement Receptor C5aR1 Inhibition Reduces Proptosis in hDPP4-Transgenic Mice Infected with MERS-CoV. Viruses. 2019; 11(1):39. https://doi.org/10.3390/v11010039
- Chen IY, Moriyama M, Chang M, Ichinohe T. Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome. Front Microbiol. 2019; 10:50. https://doi.org/10.3389/fmicb.2019.00050
- Schurink B, Roos E, Radonic T, Barbe E, Bouman CS, de Boer HH, et al. Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. Lancet Microbe. 2020; 1(7):290–299. https://doi.org/10.1016/S2666-5247(20)30144-0
- Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020; 395(10234):1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5
- Liu X, Lieberman J. A mechanistic understanding of proptosis: the fiery death triggered by invasive infection. Adv Immunol. 2017; 135:81-117. https://doi.org/10.1016/bs.ai.2017.02.002
- Palazon- Riquelme P, Lopez- Castejon G. The inflammasomes, immune guardians at defence barriers. Immunology. 2018; 155(3):320–330. https://doi.org/10.1111/imm.12989
- Bai B, Yang Y, Wang Q, Li M, Tian C, Liu Y. NLRP3 inflammasome in endothelial dysfunction. Cell Death Dis. 2020; 11:776. https://doi.org/10.1038/s41419-020-02985-x
- Vora SM, Lieberman J, Wu H. Inflammasome activation at the crux of severe COVID-19. Nat Rev Immunol. 2021; 21:694–703. https://doi.org/10.1038/s41577-021-00588-x
- Zhang J, Wu H, Yao X, Zhang D, Zhou Y, Fu B, et al. Pyroptotic macrophages stimulate the SARS-CoV-2-associated cytokine storm. Cell Mol Immunol. 2021; 18:1305–1307. https://doi.org/10.1038/s41423-021-00665-0
- Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015; 526:666–671. https://doi.org/10.1038/nature15541
- Weihua Gong, Ying Shi, Jingjing Ren. Research progresses of molecular mechanism of proptosis and its related diseases. Immunobiology. 2020; 225(2):151884. https://doi.org/10.1016/j.imbio.2019.11.019
- Marcin Dobaczewski, Wei Chen, Nikolaos G. Frangogiannis, Transforming growth factor (TGF)-β signaling in cardiac remodeling, J Mol Cell Cardiol. 2011;51(4):600-606. https://doi.org/10.1016/j.yjmcc.2010.10.033
- Tan MS, Tan L, Jiang T. Amyloid-β induces NLRP1-dependent neuronal proptosis in models of Alzheimer’s disease. Cell Death. 2014; 5:1382. https://doi.org/10.1038/cddis.2014.348
- Jesus AA, Goldbach-Mansky R. IL-1 blockade in autoinflammatory syndromes. Annu Rev Med. 2014; 65(1):223-244. https://doi.org/10.1146/annurev-med-061512-150641
- Luo B, Li B, Wang W, Liu X, Xia Y, Zhang C, et al. NLRP3 Gene Silencing Ameliorates Diabetic Cardiomyopathy in a Type 2 Diabetes Rat Model. PLOS ONE. 2014; 9(8):104771. https://doi.org/10.1371/journal.pone.0104771
- Magna M, Pisetsky DS. The role of cell death in the pathogenesis of SLE: is proptosis the missing link?. Scand J İmmunol. 2015; 82(3):218-224. https://doi.org/10.1111/sji.12335
- Fusco R, Siracusa R, Genovese T, Cuzzocrea S, Di Paola R. Focus on the Role of NLRP3 Inflammasome in Diseases. International Journal of Molecular Sciences. 2020; 21(12):4223. https://doi.org/10.3390/ijms21124223