Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Prolonged NHE Activation may be both Cause and Outcome of Cytokine Release Syndrome in COVID-19

Author(s): Medine Cumhur Cure and Erkan Cure*

Volume 28, Issue 22, 2022

Published on: 18 July, 2022

Page: [1815 - 1822] Pages: 8

DOI: 10.2174/1381612828666220713121741

Price: $65

Abstract

The release of cytokines and chemokines such as IL‐1β, IL-2, IL-6, IL-7, IL-10, TNF-α, IFN‐γ, CCL2, CCL3, and CXCL10 is increased in critically ill patients with COVID-19. Excessive cytokine release during COVID-19 is related to increased morbidity and mortality. Several mechanisms are put forward for cytokine release syndrome during COVID-19. Here we have mentioned novel pathways. SARS-CoV-2 increases angiotensin II levels by rendering ACE2 nonfunctional. Angiotensin II causes cytokine release via AT1 and AT2 receptors. Moreover, angiotensin II potently stimulates the Na+/H+ exchanger (NHE). It is a pump found in the membranes of many cells that pumps Na+ inward and H+ outward. NHE has nine isoforms. NHE1 is the most common isoform found in endothelial cells and many cells. NHE is involved in keeping the intracellular pH within physiological limits. When the intracellular pH is acidic, NHE is activated, bringing the intracellular pH to physiological levels, ending its activity. Sustained NHE activity is highly pathological and causes many problems. Prolonged NHE activation in COVID-19 may cause a decrease in intracellular pH through H+ ion accumulation in the extracellular area and subsequent redox reactions. The activation reduces the intracellular K+ concentration and leads to Na+ and Ca2+ overload. Increased ROS can cause intense cytokine release by stimulating NF-κB and NLRP3 inflammasomes. Cytokines also cause overstimulation of NHE. As the intracellular pH decreases, SARS-CoV-2 rapidly infects new cells, increasing the viral load. This vicious circle increases morbidity and mortality in patients with COVID-19. On the other hand, SARS-CoV-2 interaction with NHE3 in intestinal tissue is different from other tissues. SARS-CoV-2 can trigger CRS via NHE3 inhibition by disrupting the intestinal microbiota. This review aimed to help develop new treatment models against SARS-CoV-2- induced CRS by revealing the possible effects of SARS-CoV-2 on the NHE.

Keywords: Na+/H+ exchanger, SARS-CoV-2, COVID-19, cytokine release syndrome, angiotensin II, intracellular pH, sodium-hydrogen antiporter.

« Previous Next »
[1]
Mittal A, Dua A, Gupta S, Injeti E. A research update: Significance of cytokine storm and diaphragm in COVID-19. Curr Res Pharmacol Drug Discov 2021; 2: 100031.
[http://dx.doi.org/10.1016/j.crphar.2021.100031] [PMID: 34870147]
[2]
Dhar SK. K V, Damodar S, Gujar S, Das M. IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: Results from meta-analysis and regression. Heliyon 2021; 7(2): e06155.
[http://dx.doi.org/10.1016/j.heliyon.2021.e06155] [PMID: 33553782]
[3]
Lu Q, Zhu Z, Tan C, et al. Changes of serum IL‐10, IL‐1β, IL‐6, MCP‐1, TNF‐α, IP‐10 and IL‐4 in COVID‐19 patients. Int J Clin Pract 2021; 75(9): e14462.
[http://dx.doi.org/10.1111/ijcp.14462] [PMID: 34107113]
[4]
Jeyakumar SM, Vajreswari A. Pharmaconutrition strategy to resolve SARS-CoV-2-induced inflammatory cytokine storm in non-alcoholic fatty liver disease: Omega-3 long-chain polyunsaturated fatty acids. World J Clin Cases 2021; 9(31): 9333-49.
[http://dx.doi.org/10.12998/wjcc.v9.i31.9333] [PMID: 34877270]
[5]
Rangappa P. Cytokine storm and immunomodulation in COVID-19. Indian J Crit Care Med 2021; 25(11): 1288-91.
[http://dx.doi.org/10.5005/jp-journals-10071-24029] [PMID: 34866828]
[6]
El-Arif G, Farhat A, Khazaal S, et al. The renin-angiotensin system: A key role in SARS-CoV-2-induced COVID-19. Molecules 2021; 26(22): 6945.
[http://dx.doi.org/10.3390/molecules26226945] [PMID: 34834033]
[7]
Kuba K, Yamaguchi T, Penninger JM. Angiotensin-converting enzyme 2 (ACE2) in the pathogenesis of ARDS in COVID-19. Front Immunol 2021; 12: 732690.
[http://dx.doi.org/10.3389/fimmu.2021.732690] [PMID: 35003058]
[8]
Alique M, Sánchez-López E, Rayego-Mateos S, Egido J, Ortiz A, Ruiz-Ortega M. Angiotensin II, via angiotensin receptor type 1/nuclear factor-κB activation, causes a synergistic effect on interleukin-1-β-induced inflammatory responses in cultured mesangial cells. J Renin Angiotensin Aldosterone Syst 2015; 16(1): 23-32.
[http://dx.doi.org/10.1177/1470320314551564] [PMID: 25354522]
[9]
Ruiz-Ortega M, Lorenzo O, Rupérez M, König S, Wittig B, Egido J. Angiotensin II activates nuclear transcription factor kappaB through AT(1) and AT(2) in vascular smooth muscle cells: Molecular mechanisms. Circ Res 2000; 86(12): 1266-72.
[http://dx.doi.org/10.1161/01.RES.86.12.1266] [PMID: 10864918]
[10]
Wolf G, Wenzel U, Burns KD, Harris RC, Stahl RA, Thaiss F. Angiotensin II activates nuclear transcription factor-kappaB through AT1 and AT2 receptors. Kidney Int 2002; 61(6): 1986-95.
[http://dx.doi.org/10.1046/j.1523-1755.2002.00365.x] [PMID: 12028439]
[11]
Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017; 2(1): 17023.
[http://dx.doi.org/10.1038/sigtrans.2017.23] [PMID: 29158945]
[12]
Sadoshima J. Cytokine actions of angiotensin II. Circ Res 2000; 86(12): 1187-9.
[http://dx.doi.org/10.1161/01.RES.86.12.1187] [PMID: 10864905]
[13]
Ratajczak MZ, Kucia M. SARS-CoV-2 infection and overactivation of Nlrp3 inflammasome as a trigger of cytokine “storm” and risk factor for damage of hematopoietic stem cells. Leukemia 2020; 34(7): 1726-9.
[http://dx.doi.org/10.1038/s41375-020-0887-9] [PMID: 32483300]
[14]
Torres-López JE, Guzmán-Priego CG, Rocha-González HI, Granados-Soto V. Role of NHE1 in nociception. Pain Res Treat 2013; 2013: 1-8.
[http://dx.doi.org/10.1155/2013/217864] [PMID: 23431433]
[15]
Jenkins EC Jr, Debnath S, Gundry S, Gundry S, Uyar U, Fata JE. Intracellular pH regulation by Na+/H+ exchanger-1 (NHE1) is required for growth factor-induced mammary branching morphogenesis. Dev Biol 2012; 365(1): 71-81.
[http://dx.doi.org/10.1016/j.ydbio.2012.02.010] [PMID: 22366186]
[16]
Cumhur Cure M, Cure E. Effects of the Na+/H+ ion exchanger on susceptibility to COVID-19 and the course of the disease. J Renin Angiotensin Aldosterone Syst 2021; 2021: 1-6.
[http://dx.doi.org/10.1155/2021/4754440] [PMID: 34285709]
[17]
Packer M. Activation and inhibition of sodium-hydrogen exchanger is a mechanism that links the pathophysiology and treatment of diabetes mellitus with that of heart failure. Circulation 2017; 136(16): 1548-59.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.030418] [PMID: 29038209]
[18]
Karmazyn M, Sostaric JV, Gan XT. The myocardial Na+/H+ exchanger: A potential therapeutic target for the prevention of myocardial ischaemic and reperfusion injury and attenuation of postinfarction heart failure. Drugs 2001; 61(3): 375-89.
[http://dx.doi.org/10.2165/00003495-200161030-00006] [PMID: 11293648]
[19]
Cao L, Yuan Z, Liu M, Stock C. (Patho-)Physiology of Na+/H+ Exchangers (NHEs) in the digestive system. Front Physiol 2020; 10: 1566.
[http://dx.doi.org/10.3389/fphys.2019.01566] [PMID: 32009977]
[20]
Ruiz-Meana M, García-Dorado D. Translational cardiovascular medicine (II). Pathophysiology of ischemia-reperfusion injury: New therapeutic options for acute myocardial infarction. Rev Esp Cardiol 2009; 62(2): 199-209.
[http://dx.doi.org/10.1016/S0300-8932(09)70162-9] [PMID: 19232193]
[21]
Tang Q, Ma J, Zhang P, Wan W, Kong L, Wu L. Persistent sodium current and Na+/H+ exchange contributes to the augmentation of the reverse Na+/Ca2+ exchange during hypoxia or acute ischemia in ventricular myocytes. Pflugers Arch 2012; 463(4): 513-22.
[http://dx.doi.org/10.1007/s00424-011-1070-y] [PMID: 22234427]
[22]
Boedtkjer E, Aalkjaer C. Intracellular pH in the resistance vasculature: Regulation and functional implications. J Vasc Res 2012; 49(6): 479-96.
[http://dx.doi.org/10.1159/000341235] [PMID: 22907294]
[23]
Lagadic-Gossmann D, Huc L, Lecureur V. Alterations of intracellular pH homeostasis in apoptosis: Origins and roles. Cell Death Differ 2004; 11(9): 953-61.
[http://dx.doi.org/10.1038/sj.cdd.4401466] [PMID: 15195071]
[24]
Németh ZH, Deitch EA, Lu Q, Szabó C, Haskó G. NHE blockade inhibits chemokine production and NF-κB activation in immunostimulated endothelial cells. Am J Physiol Cell Physiol 2002; 283(2): C396-403.
[http://dx.doi.org/10.1152/ajpcell.00491.2001] [PMID: 12107048]
[25]
Cengiz P, Kintner DB, Chanana V, et al. Sustained Na+/H+ exchanger activation promotes gliotransmitter release from reactive hippocampal astrocytes following oxygen-glucose deprivation. PLoS One 2014; 9(1): e84294.
[http://dx.doi.org/10.1371/journal.pone.0084294] [PMID: 24392123]
[26]
Deng X, Ji Z, Xu B, et al. Suppressing the Na+/H+ exchanger 1: A new sight to treat depression. Cell Death Dis 2019; 10(5): 370.
[http://dx.doi.org/10.1038/s41419-019-1602-5] [PMID: 31068571]
[27]
Xia J, Huang N, Huang H, et al. Voltage-gated sodium channel ] Nav 1.7 promotes gastric cancer progression through MACC1-mediated upregulation of NHE1. Int J Cancer 2016; 139(11): 2553-69.
[http://dx.doi.org/10.1002/ijc.30381] [PMID: 27529686]
[28]
Drumm K, Gassner B, Silbernagl S, Gekle M. Inhibition of Na superset+/H superset+ exchange decreases albumin-induced NF-kappaB activation in renal proximal tubular cell lines (OK and LLC-PK1 cells). Eur J Med Res 2001; 6(10): 422-32.
[PMID: 11698229]
[29]
Qadri SM, Su Y, Cayabyab FS, Liu L. Endothelial Na+/H+ exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal. Cardiovasc Diabetol 2014; 13(1): 134.
[http://dx.doi.org/10.1186/s12933-014-0134-7] [PMID: 25270604]
[30]
Alvarez BV, Villa-Abrille MC. Mitochondrial NHE1: A newly identified target to prevent heart disease. Front Physiol 2013; 4: 152.
[http://dx.doi.org/10.3389/fphys.2013.00152] [PMID: 23825461]
[31]
Resnick LM, Gupta RK, Sosa RE, Corbett ML, Laragh JH. Intracellular pH in human and experimental hypertension. Proc Natl Acad Sci USA 1987; 84(21): 7663-7.
[http://dx.doi.org/10.1073/pnas.84.21.7663] [PMID: 3478718]
[32]
Jimenez L, Campos Codo A, Sampaio VS, et al. Acid pH increases SARS-CoV-2 infection and the risk of death by COVID-19. Front Med (Lausanne) 2021; 8: 637885.
[http://dx.doi.org/10.3389/fmed.2021.637885] [PMID: 34490283]
[33]
Cure E, Cumhur Cure M. Strong relationship between cholesterol, low-density lipoprotein receptor, Na+/H+ exchanger, and SARS-CoV-2: This association may be the cause of death in the patient with COVID-19. Lipids Health Dis 2021; 20(1): 179.
[http://dx.doi.org/10.1186/s12944-021-01607-5] [PMID: 34895256]
[34]
Mustroph J, Hupf J, Hanses F, et al. Decreased GLUT1/NHE1 RNA expression in whole blood predicts disease severity in patients with COVID‐19. ESC Heart Fail 2021; 8(1): 309-16.
[http://dx.doi.org/10.1002/ehf2.13063] [PMID: 33215884]
[35]
Bagur R, Hajnóczky G. Intracellular Ca 2+ sensing: Its role in calcium homeostasis and signaling. Mol Cell 2017; 66(6): 780-8.
[http://dx.doi.org/10.1016/j.molcel.2017.05.028] [PMID: 28622523]
[36]
Görlach A, Bertram K, Hudecova S, Krizanova O. Calcium and ROS: A mutual interplay. Redox Biol 2015; 6: 260-71.
[http://dx.doi.org/10.1016/j.redox.2015.08.010] [PMID: 26296072]
[37]
Holliday J, Gruol DL. Cytokine stimulation increases intracellular calcium and alters the response to quisqualate in cultured cortical astrocytes. Brain Res 1993; 621(2): 233-41.
[http://dx.doi.org/10.1016/0006-8993(93)90111-Y] [PMID: 8242337]
[38]
Jia L, Delmotte P, Aravamudan B, Pabelick CM, Prakash YS, Sieck GC. Effects of the inflammatory cytokines TNF-α and IL-13 on stromal interaction molecule-1 aggregation in human airway smooth muscle intracellular Ca2+ regulation. Am J Respir Cell Mol Biol 2013; 49(4): 601-8.
[http://dx.doi.org/10.1165/rcmb.2013-0040OC] [PMID: 23713409]
[39]
Birkeland ES, Koch LM, Dechant R. Another consequence of the warburg effect? Metabolic regulation of Na+/H+ exchangers may link aerobic glycolysis to cell growth. Front Oncol 2020; 10: 1561.
[http://dx.doi.org/10.3389/fonc.2020.01561] [PMID: 32974190]
[40]
Rios EJ, Fallon M, Wang J, Shimoda LA. Chronic hypoxia elevates intracellular pH and activates Na+/H+ exchange in pulmonary arterial smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2005; 289(5): L867-74.
[http://dx.doi.org/10.1152/ajplung.00455.2004] [PMID: 15964895]
[41]
Baumeister P, Quinn TA. Altered calcium handling and ventricular arrhythmias in acute ischemia. Clin Med Insights Cardiol 2016. 10s1(Suppl 1): CMC.S39706.
[http://dx.doi.org/10.4137/CMC.S39706] [PMID: 28008297]
[42]
Mansab F, Donnelly H, Kussner A, Neil J, Bhatti S, Goyal DK. Oxygen and mortality in COVID-19 pneumonia: A comparative analysis of supplemental oxygen policies and health outcomes across 26 countries. Front Public Health 2021; 9: 580585.
[http://dx.doi.org/10.3389/fpubh.2021.580585] [PMID: 34327182]
[43]
Németh ZH, Deitch EA, Szabó C, et al. Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects against colitis. Am J Physiol Gastrointest Liver Physiol 2002; 283(1): G122-32.
[http://dx.doi.org/10.1152/ajpgi.00015.2002] [PMID: 12065299]
[44]
Rungwerth K, Schindler U, Gerl M, et al. Inhibition of Na + -H + exchange by cariporide reduces inflammation and heart failure in rabbits with myocardial infarction. Br J Pharmacol 2004; 142(7): 1147-54.
[http://dx.doi.org/10.1038/sj.bjp.0705746] [PMID: 15237093]
[45]
Rajamäki K, Nordström T, Nurmi K, et al. Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome. J Biol Chem 2013; 288(19): 13410-9.
[http://dx.doi.org/10.1074/jbc.M112.426254] [PMID: 23530046]
[46]
Rossol M, Pierer M, Raulien N, et al. Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors. Nat Commun 2012; 3(1): 1329.
[http://dx.doi.org/10.1038/ncomms2339] [PMID: 23271661]
[47]
Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis 2019; 10(2): 128.
[http://dx.doi.org/10.1038/s41419-019-1413-8] [PMID: 30755589]
[48]
Lin L, Xu L, Lv W, et al. An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS). PLoS Pathog 2019; 15(6): e1007795.
[http://dx.doi.org/10.1371/journal.ppat.1007795] [PMID: 31170267]
[49]
Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 2020; 27(6): 992-1000.e3.
[http://dx.doi.org/10.1016/j.chom.2020.04.009] [PMID: 32320677]
[50]
Gangitano E, Tozzi R, Mariani S, Lenzi A, Gnessi L, Lubrano C. Ketogenic diet for obese COVID-19 patients: Is respiratory disease a contraindication? A narrative review of the literature on ketogenic diet and respiratory function. Front Nutr 2021; 8: 771047.
[http://dx.doi.org/10.3389/fnut.2021.771047] [PMID: 34957183]
[51]
Murphy EA, Velazquez KT, Herbert KM. Influence of high-fat diet on gut microbiota. Curr Opin Clin Nutr Metab Care 2015; 18(5): 515-20.
[http://dx.doi.org/10.1097/MCO.0000000000000209] [PMID: 26154278]
[52]
Port JR, Adney DR, Schwarz B, et al. High-fat high-sugar diet-induced changes in the lipid metabolism are associated with mildly increased COVID-19 severity and delayed recovery in the Syrian hamster. Viruses 2021; 13(12): 2506.
[http://dx.doi.org/10.3390/v13122506] [PMID: 34960775]
[53]
Duan Y, Zeng L, Zheng C, et al. Inflammatory links between high fat diets and diseases. Front Immunol 2018; 9: 2649.
[http://dx.doi.org/10.3389/fimmu.2018.02649] [PMID: 30483273]
[54]
Hajer GR, van Haeften TW, Visseren FLJ. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 2008; 29(24): 2959-71.
[http://dx.doi.org/10.1093/eurheartj/ehn387] [PMID: 18775919]
[55]
Zatterale F, Longo M, Naderi J, et al. Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes. Front Physiol 2020; 10: 1607.
[http://dx.doi.org/10.3389/fphys.2019.01607] [PMID: 32063863]
[56]
Dekaboruah E, Suryavanshi MV, Chettri D, Verma AK. Human microbiome: An academic update on human body site specific surveillance and its possible role. Arch Microbiol 2020; 202(8): 2147-67.
[http://dx.doi.org/10.1007/s00203-020-01931-x] [PMID: 32524177]
[57]
Clapp M, Aurora N, Herrera L, Bhatia M, Wilen E, Wakefield S. Gut microbiota’s effect on mental health: The gut-brain axis. Clin Pract 2017; 7(4): 987.
[http://dx.doi.org/10.4081/cp.2017.987] [PMID: 29071061]
[58]
Al Bander Z, Nitert MD, Mousa A, Naderpoor N. The gut microbiota and inflammation: An overview. Int J Environ Res Public Health 2020; 17(20): 7618.
[http://dx.doi.org/10.3390/ijerph17207618] [PMID: 33086688]
[59]
DeGruttola AK, Low D, Mizoguchi A, Mizoguchi E. Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis 2016; 22(5): 1137-50.
[http://dx.doi.org/10.1097/MIB.0000000000000750] [PMID: 27070911]
[60]
Rutsch A, Kantsjö JB, Ronchi F. The gut-brain axis: How microbiota and host inflammasome influence brain physiology and pathology. Front Immunol 2020; 11: 604179.
[http://dx.doi.org/10.3389/fimmu.2020.604179] [PMID: 33362788]
[61]
Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol 2015; 28(2): 203-9.
[PMID: 25830558]
[62]
Ghaisas S, Maher J, Kanthasamy A. Gut microbiome in health and disease: Linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacol Ther 2016; 158: 52-62.
[http://dx.doi.org/10.1016/j.pharmthera.2015.11.012] [PMID: 26627987]
[63]
Yiu JHC, Dorweiler B, Woo CW. Interaction between gut microbiota and toll-like receptor: From immunity to metabolism. J Mol Med (Berl) 2017; 95(1): 13-20.
[http://dx.doi.org/10.1007/s00109-016-1474-4] [PMID: 27639584]
[64]
Saad MJA, Santos A, Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology (Bethesda) 2016; 31(4): 283-93.
[http://dx.doi.org/10.1152/physiol.00041.2015] [PMID: 27252163]
[65]
Gurney MA, Laubitz D, Ghishan FK, Kiela PR. Pathophysiology of intestinal Na+/H+ exchange. Cell Mol Gastroenterol Hepatol 2017; 3(1): 27-40.
[http://dx.doi.org/10.1016/j.jcmgh.2016.09.010] [PMID: 28090568]
[66]
Harrison CA, Laubitz D, Ohland CL, et al. Microbial dysbiosis associated with impaired intestinal Na+/H+ exchange accelerates and exacerbates colitis in ex-germ free mice. Mucosal Immunol 2018; 11(5): 1329-41.
[http://dx.doi.org/10.1038/s41385-018-0035-2] [PMID: 29875400]
[67]
Zachos NC, Tse M, Donowitz M. Molecular physiology of intestinal Na+/H+ exchange. Annu Rev Physiol 2005; 67(1): 411-43.
[http://dx.doi.org/10.1146/annurev.physiol.67.031103.153004] [PMID: 15709964]
[68]
Nwia SM, Li XC, Leite APO, Hassan R, Zhuo JL. The Na+/H+ exchanger 3 in the intestines and the proximal tubule of the kidney: Localization, physiological function, and key roles in angiotensin II-induced hypertension. Front Physiol 2022; 13: 861659.
[http://dx.doi.org/10.3389/fphys.2022.861659] [PMID: 35514347]
[69]
Li T, Tuo B. Pathophysiology of hepatic Na+/H+ exchange. Exp Ther Med 2020; 20(2): 1220-9.
[http://dx.doi.org/10.3892/etm.2020.8888] [PMID: 32742358]
[70]
Uthman L, Li X, Baartscheer A, et al. Empagliflozin reduces oxidative stress through inhibition of the novel inflammation/] NHE/[Na+]c/ROS-pathway in human endothelial cells. Biomed Pharmacother 2022; 146: 112515.
[http://dx.doi.org/10.1016/j.biopha.2021.112515] [PMID: 34896968]
[71]
Amin MR, Malakooti J, Sandoval R, Dudeja PK, Ramaswamy K. IFN-γ and TNF-α regulate human NHE3 gene expression by modulating the Sp family transcription factors in human intestinal epithelial cell line C2BBe1. Am J Physiol Cell Physiol 2006; 291(5): C887-96.
[http://dx.doi.org/10.1152/ajpcell.00630.2005] [PMID: 16760259]
[72]
He P, Yun CC. Mechanisms of the regulation of the intestinal Na+/H+ exchanger NHE3. J Biomed Biotechnol 2010; 2010: 1-10.
[http://dx.doi.org/10.1155/2010/238080] [PMID: 20011065]
[73]
Hodges K, Alto NM, Ramaswamy K, Dudeja PK, Hecht G. The enteropathogenic Escherichia coli effector protein EspF decreases sodium hydrogen exchanger 3 activity. Cell Microbiol 2008; 10(8): 1735-45.
[http://dx.doi.org/10.1111/j.1462-5822.2008.01163.x] [PMID: 18433466]
[74]
Hernández-Terán A, Mejía-Nepomuceno F, Herrera MT, et al. Dysbiosis and structural disruption of the respiratory microbiota in COVID-19 patients with severe and fatal outcomes. Sci Rep 2021; 11(1): 21297.
[http://dx.doi.org/10.1038/s41598-021-00851-0] [PMID: 34716394]
[75]
Rafiqul Islam SM, Foysal MJ, Hoque MN, et al. Dysbiosis of oral and gut microbiomes in SARS-CoV-2 infected patients in Bangladesh: Elucidating the role of opportunistic gut microbes. Front Med (Lausanne) 2022; 9: 821777.
[http://dx.doi.org/10.3389/fmed.2022.821777] [PMID: 35237631]
[76]
Parasa S, Desai M, Thoguluva Chandrasekar V, et al. Prevalence of gastrointestinal symptoms and fecal viral shedding in patients with coronavirus disease 2019. JAMA Netw Open 2020; 3(6): e2011335.
[http://dx.doi.org/10.1001/jamanetworkopen.2020.11335] [PMID: 32525549]
[77]
Zhang L, Han C, Zhang S, et al. Diarrhea and altered inflammatory cytokine pattern in severe coronavirus disease 2019: Impact on disease course and in‐hospital mortality. J Gastroenterol Hepatol 2021; 36(2): 421-9.
[http://dx.doi.org/10.1111/jgh.15166] [PMID: 32602128]
[78]
Darif D, Hammi I, Kihel A, El Idrissi Saik I, Guessous F, Akarid K. The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong? Microb Pathog 2021; 153: 104799.
[http://dx.doi.org/10.1016/j.micpath.2021.104799] [PMID: 33609650]
[79]
Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med 2021; 384(8): 693-704.
[http://dx.doi.org/10.1056/NEJMoa2021436] [PMID: 32678530]
[80]
Gareb B, Otten AT, Frijlink HW, Dijkstra G, Kosterink JGW. Review: Local tumor necrosis factor-α inhibition in inflammatory bowel disease. Pharmaceutics 2020; 12(6): 539.
[http://dx.doi.org/10.3390/pharmaceutics12060539] [PMID: 32545207]
[81]
Kokkotis G, Kitsou K, Xynogalas I, et al. Systematic review with meta‐analysis: COVID‐19 outcomes in patients receiving anti‐TNF treatments. Aliment Pharmacol Ther 2022; 55(2): 154-67.
[http://dx.doi.org/10.1111/apt.16717] [PMID: 34881430]
[82]
Guo Y, Hu K, Li Y, et al. Targeting TNF-α for COVID-19: Recent advanced and controversies. Front Public Health 2022; 10: 833967.
[http://dx.doi.org/10.3389/fpubh.2022.833967] [PMID: 35223745]

Rights & Permissions Print Cite
Article Metrics
18
1
© 2024 Bentham Science Publishers | Privacy Policy