IL-1 beta-stimulated leucocyte-endothelial adhesion is regulated, in part, by the cyclic-GMP-dependent signal transduction pathway.
It is well known that the exposure of endothelial cells to IL-1 beta induces an increase in endothelial cell adhesiveness for leucocytes. Using rat heart endothelial cells we found that exposure of endothelial cells to IL-1 beta (100 U/ml) induces a 133-fold increase in the intracellular concentration of cyclic-GMP; from 11.5 +/- 0.2 fM to 1530 +/- 117.8 fM (per 10(6) cells). Therefore, we examined whether cyclic-GMP is involved in the regulation of endothelial adhesiveness for leucocytes. Cyclic-GMP analogue, dibutyryl cyclic-GMP Methylene blue, an inhibitor of guanylate cyclaese, and KT5823, a specific inhibitor of cyclic-GMP-dependent protein kinase, inhibited both basal as well as IL-1 beta-induced endothelial cell adhesiveness for leucocytes, and KT5823 abolished the dibutyryl-cyclic-GMP-induced increase in endothelial adhesiveness. The effect of cyclic-GMP, induced by IL-1 beta treatment, on the endothelial adhesiveness may be either direct or indirect because of the time-gap between the rise in cyclic-GMP level and the increase of endothelial adhesiveness. IL-1 beta (100 U/ml) and dibutyryl-cyclic-GMP (0.01 mM) both induced an increase in the expression of intercellular adhesion molecule-1 by endothelial cells. However, the fact that KT5823 failed to prevent this increase, suggests that, although the IL-1 beta-induced increase in adhesiveness is caused by the increase in intracellular levels of cyclic-GMP, it may not be mediated through intercellular adhesion molecule-1. In conclusion, the results obtained indicate that endothelial cell adhesiveness for leucocytes is, in part, regulated by the cyclic-GMP-dependent signal transduction pathway.
Leszczynski
D
D
Department of Research, Finnish Centre for Radiation and Nuclear Safety, Helsinki.
Josephs
M D
MD
Foegh
M L
ML
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002460:Cell Line; D006152:Cyclic GMP / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005434:Flow Cytometry; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D018799:Intercellular Adhesion Molecule-1; D006152:Cyclic GMP