MALFORMIN-A1 INHIBITS THE BINDING OF INTERLEUKIN-1-BETA (IL1-BETA) AND SUPPRESSES THE EXPRESSION OF TISSUE FACTOR IN HUMAN ENDOTHELIAL-CELLS AND MONOCYTES

被引：13

作者：

HERBERT, JM ^{[1
]}

SAVI, P ^{[1
]}

LALE, A ^{[1
]}

LAPLACE, MC ^{[1
]}

BAUDRY, N ^{[1
]}

PEREILLO, JM ^{[1
]}

EMONDSALT, X ^{[1
]}

机构：

[1] SANOFI RECH, MONTPELLIER, FRANCE

来源：

BIOCHEMICAL PHARMACOLOGY | 1994年 / 48卷 / 06期

关键词：

MALFORMIN-A1; INTERLEUKIN-1; MONOCYTES; ENDOTHELIUM; TISSUE FACTOR;

D O I：

10.1016/0006-2952(94)90158-9

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Malformin-A1, a cyclic pentapeptide of microbial origin, antagonized in a competitive manner the binding of I-125-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.

引用

页码：1211 / 1217

页数：7

共 47 条

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[2] HETEROGENEOUS REGULATION OF CONSTITUTIVE THROMBOMODULIN OR INDUCIBLE TISSUE-FACTOR ACTIVITIES ON THE SURFACE OF HUMAN SAPHENOUS-VEIN ENDOTHELIAL-CELLS IN CULTURE FOLLOWING STIMULATION BY INTERLEUKIN-1, TUMOR-NECROSIS-FACTOR, THROMBIN OR PHORBOL ESTER [J].