Fibroblast growth factor and heparin protect endothelial cells from the effects of interleukin 1.
Vascular endothelium is involved in both active and passive processes in haemostasis, but inflammatory cytokines such as interleukin 1 (IL-1) and tumour necrosis factor (TNF) have been reported to convert the comparatively inert endothelial cell to an inflammatory state. Acidic fibroblast growth factor (aFGF) in the presence of heparin has effects opposite to IL-1 on cultured human umbilical vein endothelial cells (HUVEC); therefore, we have investigated the modulation of IL-1-induced effects by the c combination of aFGF and heparin (aFGF/heparin). First passage HUVEC were cultured for 6 days in the presence of 20% human serum with and without the addition of 625 pM human recombinant aFGF (hr aFGF) and 7 microM heparin. On day 5, recombinant IL-1 beta was included for 24 h. The following day the cells were washed and measurements made of the release of prostacyclin, von Willebrand factor, plasminogen activator inhibitor type 1, and thrombospondin, both in the resting state and following stimulation for 60 min with 1 U/ml thrombin. Tissue-type plasminogen activator was assayed in HUVEC lysates. Similar experiments were performed to assess effects on the expression of vascular adhesion molecule, intracellular adhesion molecule, and E-selectin using an ELISA on cells in situ. This study indicates that aFGF/heparin in the culture medium of HUVEC abrogates the measured responses to IL-1. These data imply that routine endothelial cell culture with aFGF/heparin may cause artefacts, the effects of FGF and Il-1 may involve common pathways, and FGF/heparin may offer an approach to design therapeutics to counter the adverse effects of IL-1.
Minter
A J
AJ
Centre for Thrombosis and Vascular Research, University of New South Wales, Prince of Wales Hospital, Sydney, Australia.
Keoshkerian
E
E
Chesterman
C N
CN
Dawes
J
J
D015815:Cell Adhesion Molecules / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000494:pharmacology; D019699:Thrombospondins; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014470:Umbilical Cord / Q000166:cytology; D014841:von Willebrand Factor / Q000378:metabolism
D015815:Cell Adhesion Molecules; D005343:Fibrinolytic Agents; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D017395:Plasminogen Activator Inhibitor 1; D019699:Thrombospondins; D014841:von Willebrand Factor; D005346:Fibroblast Growth Factors; D006493:Heparin; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator