Malformin-A1 inhibits the binding of interleukin-1 beta (IL1 beta) and suppresses the expression of tissue factor in human endothelial cells and monocytes.
Malformin-A1, a cyclic pentapeptide of microbial origin, antagonized in a competitive manner the binding of 125I-IL1 beta (interleukin-1 beta) to human monocytes and cultured human umbilical vein endothelial cells (HUVEC) with IC50 values (doses which reduce specific binding by 50%) of 250 +/- 80 and 230 +/- 25 nM, respectively (N = 3). IL1 increased in a dose-dependent manner the expression of tissue factor, a ubiquitous membrane-anchored glycoprotein that initiates blood coagulation at the surface of HUVEC and human monocytes. Malformin-A1 strongly inhibited IL1-induced tissue factor expression in HUVEC and monocytes with IC50 values of 420 +/- 35 and 105 +/- 25 nM, respectively (N = 3), and reduced IL1-induced expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on HUVEC (IC50 = 125 +/- 18 nM) (N = 4). These observations demonstrate that malformin-A1 recognizes and blocks IL1 beta binding to its receptor sites on monocytes and endothelial cells and protects these cells from IL1-induced procoagulant changes.
Herbert
J M
JM
Sanofi Recherche, Toulouse, France.
Savi
P
P
Lalé
A
A
Laplace
M C
MC
Baudry
N
N
Pereillo
J M
JM
Emonds-Alt
X
X
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D007457:Iodine Radioisotopes; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013925:Thromboplastin / Q000378:metabolism*
D007375:Interleukin-1; D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; D017472:Receptors, Interleukin-1; D018799:Intercellular Adhesion Molecule-1; C001675:malformins; D013925:Thromboplastin