INTERLEUKIN-1-ALPHA 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 v ivo, cultured endothelial cells from the IVC did express Thy-1, thereb y suggesting that the expression was acquired during cultivation of th e cells in vitro, possibly by autoactivation by cytokine-like substanc es. Interleukin (IL)-1 alpha 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-1 alpha by REC was augmented by exogenously added IL-1 alpha, thereby implying the p resence of autocrine regulation by IL-1 alpha. The unaltered expressio n of Thy-1 by exogenously added IL-1 alpha suggests that Thy-1 express ion on REC had already been maximally induced by autologous cytokines; the expression of Thy-1 on REC was lowered by inhibiting protein kina se C and by depleting IL-1 alpha activity from culture supernatants. A lthough cytokine-like regulators, other than IL-1 alpha, 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-1 alpha in vitro. Moreover, Thy -1 expression was induced on rat vascular endothelium at the subcutis where recombinant IL-1 alpha was injected. The evidence indicates that IL-1 alpha functions as one regulator responsible for the induction o f Thy-1 on REC, in vitro as well as in vivo. (C) 1997 Academic Press.