Ouabain reduces the expression of the adhesion molecule CD18 in neutrophils

Cavalcante‐Silva, Luiz Henrique Agra; Lima, Éssia de Almeida; Carvalho, Deyse Cristina Madruga; Rodrigues‐Mascarenhas, Sandra

doi:10.1007/s10787-019-00602-8

Cited by 7 publications

(7 citation statements)

References 49 publications

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“…The classic cell recruitment generally follows a stepwise model, including tethering, rolling, adhesion, crawling, and transmigration step (Kolaczkowska and Kubes 2013 ; Liew and Kubes 2019 ). A previous study showed that ouabain could interfere with the adhesion step since it reduces CD18 adhesion molecule expression (Cavalcante-Silva et al 2020 ). In the transwell model, cells added in the upper compartment can migrate through a porous membrane to the lower chamber due to a chemotactic gradient.…”

Section: Discussionmentioning

confidence: 99%

“…Neutrophils were isolated as previously described (Mocsai et al 2003 ; Cavalcante-Silva et al 2020 ). Neutrophil chemotaxis was assessed using a transwell system.…”

Section: Methodsmentioning

confidence: 99%

“…Other studies have also reported this activity in human neutrophils (Ray and Samanta 1997 ). The impairment of neutrophil migration by ouabain could be related to reduced CD18 expression, an integrin beta-2 chain (Cavalcante-Silva et al 2020 ). Cardiotonic steroids inhibit Na + /K + -ATPase (NKA) and alter cellular ion concentration.…”

Section: Introductionmentioning

confidence: 99%

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Ouabain inhibits p38 activation in mice neutrophils

et al. 2021

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Section: Discussionmentioning

confidence: 99%

“…Neutrophils were isolated as previously described (Mocsai et al 2003 ; Cavalcante-Silva et al 2020 ). Neutrophil chemotaxis was assessed using a transwell system.…”

Section: Methodsmentioning

confidence: 99%

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Ouabain inhibits p38 activation in mice neutrophils

et al. 2021

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“…CGs act on leukocytes that inhibit cell proliferation, migration, and the production of proinflammatory cytokines (Cavalcante-Silva et al, 2017;Furst et al, 2017;Cavalcante-Silva et al, 2020). CGs inhibit NFκB (Yang et al, 2005) and reduce viral entry into lung epithelial cells, directly decreasing proinflammatory cytokine production (Mahase, 2020).…”

Section: Cgs As Anti-inflammatory Drugsmentioning

confidence: 99%

“…In vivo, CG also has an anti-inflammatory role. Ouabain inhibits CD18 expression in monocytes; CD18 is an adhesion molecule involved in monocyte migration to the inflammatory site of injury (Cavalcante-Silva et al, 2020). Ouabain also reduces fluid extravasation, leukocyte infiltration, and the levels of the cytokines IL-1β and TNFα in mice with zymosan-induced peritonitis (Leite et al, 2015).…”

Section: Cgs As Anti-inflammatory Drugsmentioning

confidence: 99%

Na+/K+-ATPase as a Target of Cardiac Glycosides for the Treatment of SARS-CoV-2 Infection

et al. 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified for the first time in Wuhan, China, causes coronavirus disease 2019 (COVID-19), which moved from epidemic status to becoming a pandemic. Since its discovery in December 2019, there have been countless cases of mortality and morbidity due to this virus. Several compounds such as chloroquine, hydroxychloroquine, lopinavir-ritonavir, and remdesivir have been tested as potential therapies; however, no effective treatment is currently recommended by regulatory agencies. Some studies on respiratory non-enveloped viruses such as adenoviruses and rhinovirus and some respiratory enveloped viruses including human respiratory syncytial viruses, influenza A, parainfluenza, SARS-CoV, and SARS-CoV-2 have shown the antiviral activity of cardiac glycosides, correlating their effect with Na+/K+-ATPase (NKA) modulation. Cardiac glycosides are secondary metabolites used to treat patients with cardiac insufficiency because they are the most potent inotropic agents. The effects of cardiac glycosides on NKA are dependent on cell type, exposure time, and drug concentration. They may also cause blockage of Na+ and K+ ionic transport or trigger signaling pathways. The antiviral activity of cardiac glycosides is related to cell signaling activation through NKA inhibition. Nuclear factor kappa B (NFκB) seems to be an essential transcription factor for SARS-CoV-2 infection. NFκB inhibition by cardiac glycosides interferes directly with SARS-CoV-2 yield and inflammatory cytokine production. Interestingly, the antiviral effect of cardiac glycosides is associated with tyrosine kinase (Src) activation, and NFκB appears to be regulated by Src. Src is one of the main signaling targets of the NKA α-subunit, modulating other signaling factors that may also impair viral infection. These data suggest that Src-NFκB signaling modulated by NKA plays a crucial role in the inhibition of SARS-CoV-2 infection. Herein, we discuss the antiviral effects of cardiac glycosides on different respiratory viruses, SARS-CoV-2 pathology, cell signaling pathways, and NKA as a possible molecular target for the treatment of COVID-19.

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