Transforming growth factor-beta1 inhibits thrombin activation of endothelial cells.
Transforming growth factor-beta1 (TGF-beta1) is reported to exert both pro- and anti-inflammatory effects on the chronic activation of endothelial cells (ECs) in vitro by cytokines such as tumour necrosis factor-alpha (TNF-alpha). However, the effects of TGF-beta1 on acute inflammatory responses of ECs in vitro (e.g. to thrombin) have not been characterised. Pretreatment with TGF-beta1 (10 ng/mL) effectively inhibited all the thrombin-stimulated responses in rat aortic endothelial cells (RAECs) examined: adhesion and migration of polymorphonuclear leukocytes, adhesion of platelets and lymphocytes. Substantial inhibition of thrombin stimulation occurred after 30 min of pretreatment with TGF-beta1 and maximal inhibition was obtained after 1-20 h of pretreatment. Inhibition by TGF-beta1 pretreatment for 30 min was not affected by cycloheximide and was therefore independent of protein synthesis. Treatment with TGF-beta1 for 20 h did not affect the total levels of P-selectin and von Willebrand factor (vWF) in RAECs, but reduced thrombin-stimulated recruitment of P-selectin and vWF to the cell surface. The data demonstrate that TGF-beta1 exerts a potent anti-thrombin effect on ECs, effective after long and short pretreatment times.
Harris
Harriet
H
Section of Cardiovascular Biology, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK. hhl@mole.bio.cam.ac.uk
Kirschenlohr
Heide
H
Szabados
Nicole
N
Metcalfe
James
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000276:immunology; D013917:Thrombin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology; D053773:Transforming Growth Factor beta1; D014841:von Willebrand Factor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D044463:Receptor, PAR-1; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014841:von Willebrand Factor; D003513:Cycloheximide; D013917:Thrombin