Abstract
Cardiotonic steroids are natural compounds that present many physiological and pharmacological functions. They bind Na+/K+-ATPase (NKA) modifying cellular ion concentration and trigger cell signaling mechanisms without altering ion balance. These steroids are known to modulate some immune responses, including cytokine production, neutrophil migration, and inflammation (peripherally and in the nervous system). Inflammation can occur in response to homeostasis perturbations and is related to the development of many diseases, including immune-mediated diseases and neurodegenerative disorders. Considering the neutrophils role in the general neuroinflammatory response and that these cells can be modulated by cardiac steroids, this work aims to review the possible regulation of neutrophilic neuroinflammation by the cardiac steroid ouabain.
Highlights
Jacqueline Alves Leite 1†, Luiz Henrique Agra Cavalcante-Silva 2†, Martina Raissa Ribeiro 3, Geovanni de Morais Lima 3, Cristoforo Scavone 3* and Sandra Rodrigues-Mascarenhas 2
Specialty section: This article was submitted to Inflammation Pharmacology, a section of the journal Frontiers in Pharmacology
Considering the neutrophils role in the general neuroinflammatory response and that these cells can be modulated by cardiac steroids, this work aims to review the possible regulation of neutrophilic neuroinflammation by the cardiac steroid ouabain
Summary
At low concentrations (usually at nanomolar range), ouabain can promote conformational changes in NKA, without inhibiting the transport of sodium and potassium (Liu et al, 2000; Xie, 2003). This process leads to the activation/inhibition of many cell signaling proteins, including Src, MAPKs, and NF-κB (Cui and Xie, 2017). Dysregulated migration or activation of inflammatory cells, such as neutrophils are involved in the immunopathogenesis of many diseases (Leliefeld et al, 2016; Hellebrekers et al, 2018; Cavalcante-Silva et al, 2021b; Bautista-Becerril et al, 2021; Parackova et al, 2021) Modulating these cells can be a therapeutic approach for inflammatory diseases. The ouabain effect on neutrophil during peripheral and neuro inflammation will be discussed below
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