TRANSFORMING GROWTH-FACTOR-BETA-1 INHIBITS CYTOKINE-INDUCED CNS ENDOTHELIAL-CELL ACTIVATION

Postcapillary endothelium at the sites of inflammation undergoes a ser ies of changes collectively termed endothelial cell activation. Activa ted endothelium expresses immunologically relevant surface proteins th at include MHC class II antigens (Ags) and adhesion proteins, as well as exhibits a number of functional changes. Endothelial activation has not been thoroughly studied in CNS endothelium. We have examined cyto kine-mediated endothelial activation in isolated rat CNS microvessels: Freshly isolated rat CNS microvessels are viable in culture for at le ast 72 h; Untreated microvessels express no endothelial activation ant igens; but do exhibit constitutive expression of the transferrin recep tor (tfR). INF gamma induces a dose-dependent increase in both MHC cla ss II antigens and tfR measured by immunofluorescent staining and quan titated by laser cytometry. IFN gamma-mediated endothelial cell activa tion could be inhibited with as little as 2 ng/mL TGF-beta 1, although 100% inhibition was seen with 10 ng/mL TGF-beta 1. Cytokine-preactiva ted endothelial expression of class II Ag and tfR could also be inhibi ted by TGF-beta 1. TGF-beta 1-treated microvessels become anergic to I FN gamma stimulation. Results suggest that TGF-beta 1 may have a regul atory role in endothelial activation.