Interleukin-1alpha regulates Thy-1 expression on rat vascular endothelial cells.

We recently reported that Thy-1, a surface molecule induced on the rat endothelium, regulates vascular permeability at sites of inflammation. Although the rat inferior vena cava (IVC) did not express Thy-1 in vivo, cultured endothelial cells from the IVC did express Thy-1, thereby suggesting that the expression was acquired during cultivation of the cells in vitro, possibly by autoactivation by cytokine-like substances. Interleukin (IL)-1alpha but not tumor necrosis factor (TNF)-alpha or interferon (IFN)-gamma was detected in culture supernatants of rat endothelial cells (REC) by ELISA. The production of IL-1alpha by REC was augmented by exogenously added IL-1alpha, thereby implying the presence of autocrine regulation by IL-1alpha. The unaltered expression of Thy-1 by exogenously added IL-1alpha suggests that Thy-1 expression on REC had already been maximally induced by autologous cytokines; the expression of Thy-1 on REC was lowered by inhibiting protein kinase C and by depleting IL-1alpha activity from culture supernatants. Although cytokine-like regulators, other than IL-1alpha, TNF-alpha, or IFN-gamma, produced by REC may also modulate the expression of Thy-1, it is at least in part mediated by IL-1alpha in vitro. Moreover, Thy-1 expression was induced on rat vascular endothelium at the subcutis where recombinant IL-1alpha was injected. The evidence indicates that IL-1alpha functions as one regulator responsible for the induction of Thy-1 on REC, in vitro as well as in vivo.