K Ihenetu1, R Espinosa, R de Leon, G Planas, A Perez-Pinero, L Waldbeser. 1. Department of Life Sciences/Division of Biomedical and Molecular Science, Texas A&M University-Corpus Christi, 6300 Ocean Dr., Unit 5802, 78412, Corpus Christi, Texas, USA. Kenneth.ihenetu@tamucc.edu
Abstract
OBJECTIVE: Cardiac glycosides such as digoxin and their endogenous counterpart digoxin-like immunoreactive factor (DLIF) may possess anti-inflammatory properties. METHODS: Pro-inflammatory cytokines from human peripheral blood mononuclear cells (PBMC) were measured by ELISA using specific antibodies. Immunocytochemistry was used to localize NF-K: B. RESULTS: Non-stimulated PBMC constitutively secreted minimum amounts of cytokines. LPS (1 mg/L) stimulation lead to steep increases in TNF-alpha, IL-6 and IL-8 concentrations with peak rises at 8 h. An 8 h delay was observed for IL-10. Increases in IL-10 were sustained for18 h period. Significant inhibition (P > 0.05) of TNF-alpha, IL-6 and IL-8 at non-toxic of digoxin concentration (< 100 nM) and DLIF (10 nM digoxin equivalent (de)) was observed whereas no such effect was seen for IL-10. Inhibition of the degradation of activated NF-K: B in the PBMC was observed with the indicated concentrations of digoxin, DLIF or Pyrrolidine dithiocarbamate (PDTC). CONCLUSION: Digoxin and DLIF inhibit the release of proinflammatory cytokines from PBMC via NF-K: B-dependent pathway suggesting an anti-inflammatory effect.
OBJECTIVE: Cardiac glycosides such as digoxin and their endogenous counterpart digoxin-like immunoreactive factor (DLIF) may possess anti-inflammatory properties. METHODS: Pro-inflammatory cytokines from human peripheral blood mononuclear cells (PBMC) were measured by ELISA using specific antibodies. Immunocytochemistry was used to localize NF-K: B. RESULTS: Non-stimulated PBMC constitutively secreted minimum amounts of cytokines. LPS (1 mg/L) stimulation lead to steep increases in TNF-alpha, IL-6 and IL-8 concentrations with peak rises at 8 h. An 8 h delay was observed for IL-10. Increases in IL-10 were sustained for18 h period. Significant inhibition (P > 0.05) of TNF-alpha, IL-6 and IL-8 at non-toxic of digoxin concentration (< 100 nM) and DLIF (10 nM digoxin equivalent (de)) was observed whereas no such effect was seen for IL-10. Inhibition of the degradation of activated NF-K: B in the PBMC was observed with the indicated concentrations of digoxin, DLIF or Pyrrolidine dithiocarbamate (PDTC). CONCLUSION:Digoxin and DLIF inhibit the release of proinflammatory cytokines from PBMC via NF-K: B-dependent pathway suggesting an anti-inflammatory effect.
Authors: Nicholas Parkinson; Natasha Rodgers; Max Head Fourman; Bo Wang; Marie Zechner; Maaike C Swets; Jonathan E Millar; Andy Law; Clark D Russell; J Kenneth Baillie; Sara Clohisey Journal: Sci Rep Date: 2020-12-18 Impact factor: 4.379
Authors: Hesham R El-Seedi; Nermeen Yosri; Bishoy El-Aarag; Shaymaa H Mahmoud; Ahmed Zayed; Ming Du; Aamer Saeed; Syed G Musharraf; Islam M El-Garawani; Mohamed R Habib; Haroon Elrasheid Tahir; Momtaz M Hegab; Xiaobo Zou; Zhiming Guo; Thomas Efferth; Shaden A M Khalifa Journal: Molecules Date: 2022-10-05 Impact factor: 4.927