Digibind attenuates cytokine TNFalpha-induced endothelial inflammatory response: potential benefit role of digibind in preeclampsia.
OBJECTIVE
Exaggerated inflammatory response occurs in preeclampsia. Preeclampsia is also associated with elevated endogenous digoxin-like factors (EDLFs). Clinical data suggest that Digibind (a polyclonal sheep digoxin binding Fab fragment) binds to EDLF and may have the potential to attenuate vasoconstriction and other clinical symptoms of preeclampsia. This study was undertaken to determine if Digibind could attenuate increased endothelial inflammatory response induced by tumor necrosis factor-alpha (TNFalpha).


METHODS
Confluent endothelial cells were treated with TNFalpha at different concentrations with or without Digibind in culture. Endothelial adhesion molecule ICAM, VCAM and E-selectin expressions were determined by an immunoassay directly detected on the endothelial surface. Effects of Digibind on TNFalpha-induced extracellular signal-regulated kinase and Na(+)/K(+)-ATPase expressions were also examined.


RESULTS
(1) TNFalpha induced dose-dependent increases in ICAM, VCAM and E-selectin expressions in endothelial cells; (2) Digibind could attenuate and reduce TNFalpha-induced upregulation of endothelial E-selectin, ICAM and VCAM expressions. The blocking effect was in a concentration dependent manner; (3) Digibind had no effects on TNFalpha-induced upregulation of extracellular signal-regulated kinase phosphorylation, but could block TNFalpha-induced downregulation of Na(+)/K(+)-ATPase beta1 expression.


CONCLUSIONS
Digibind may exert beneficial effects by preserving cell membrane Na(+)/K(+)-ATPase function and consequently to offset increased inflammatory response in endothelial cells.
Wang
Y
Y
Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. ywang1@lsuhsc.edu
Lewis
D F
DF
Adair
C D
CD
Gu
Y
Y
Mason
L
L
Kipikasa
J H
JH
D015815:Cell Adhesion Molecules / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D015331:Cohort Studies; D004077:Digoxin / Q000276:immunology; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology
D015815:Cell Adhesion Molecules; D007140:Immunoglobulin Fab Fragments; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; C050199:digoxin antibodies Fab fragments; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase