Echinomycin suppresses the pyrogenic effects of endotoxin and interleukin-1 beta in human endothelial cells and peripheral blood mononuclear cells.
Endotoxin (LPS) and interleukin-1 beta (IL-1 beta) increased in a dose-dependent manner the expression of tissue factor, an ubiquitous membrane-anchored glycoprotein that initiates blood coagulation at the surface of human umbilical vein endothelial cells (HUVEC and human peripheral blood mononuclear cells (PBMC). Echinomycin, a cyclic octapeptide of microbial origin strongly inhibited LPS- and IL-1 beta-induced tissue factor expression in HUVEC and PBMC with IC50 values in the subnanomolar range at the same time it reduced LPS and IL-1 beta-induced expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on HUVEC (IC50 = 0.4 +/- 0.1 and 0.3 +/- 0.2 nM respectively). Echinomycin also reduced LPS-induced secretion of IL-1 beta and IL-6 by human PBMC (IC50 = 10 +/- 2 and 3 +/- 0.5 nM respectively). These observations demonstrate that echinomycin protects endothelial cells and PBMC from the pyrogenic effect of LPS and IL-1 beta.
Herbert
J M
JM
Sanofi Recherche, Toulouse, France.
Lalé
A
A
Pereillo
J M
JM
Derocq
J M
JM
Casellas
P
P
D004448:Echinomycin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D011749:Pyrogens / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics
D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D011749:Pyrogens; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D004448:Echinomycin; D013925:Thromboplastin