The Effect of Dexamethasone and Transforming Growth Factor-beta1 on the Cytokine Induced Expression of VCAM-1 in Glomerular Endothelial Cells / 대한신장학회잡지

ABSTRACT

Endothelial cell have been shown to play an active role in many phases of immunologic process, including binding of T lymphocytes, neutrophils, platelets, and monocytes to the endothelium, as well as phagocytosis. Endothelial cells can also serve as targets that undergo cell injury. The most prominent mediators of endothelial cell activation are IL-1beta and TNF-alpha. VLA-4 was first identified as an endothelial cell surface receptor. We performed the culture of endothelial cells derived from human glomerular capillaries and studied the cytokine-regulated expression of VCAM-1, and the effect of dexamethasone and TGF-beta on the cytokine induced VCAM-1 expression using ELISA method. Expression of VCAM-1 was not detectable above background level in the basal unstimulated state. However, VCAM-1 was rapidly induced after exposure to IL-1beta (5ng/ml) or TNF-alpha (1, 10ng/ml) (O.D.=1.76+/-0.15, 1.95+/-0.35, 1.88+/-0.17, mean+/-S.E., control=0.36+/-0.028, n=8-24, P<0.05). But IFN-gamma did not increase the expression of VCAM-1. Addition of dexamethasone (10 micrometer) and TGF-beta1 (1ng, 10ng/ml) blunted IL-1beta and TNF-alpha induced expression of VCAM-1. Therefore, VCAM-1 could be inducible in human glomerular endothelial cells, and it was regulated by dexamethasone and TGF-beta1. The negative findings in histopathology may reflect the transience of VCAM-1 expression and does not necessarily exclude an important role of this molecule in the early stages of renal disease.