DIFFERENTIAL-EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA-1 ON LIPOPOLYSACCHARIDE INDUCTION OF ENDOTHELIAL ADHESION MOLECULES

In this report, we studied the effects of transforming growth factor ( TGF)-beta 1 on lipopolysaccharide (LPS)-induced expression of endothel ial cell (EC) adhesion molecules. Confluent human umbilical cord vein EC cultures were stimulated with Escherichia coli LPS and TGF-beta 1, alone or in combination for various times and evaluated for expression of ICAM-1, E-selectin, and VCAM-1 by immunofluorescence and radioimmu noassay. Effects of LPS and/or TGF-beta 1 on cell growth were also stu died by H-3-thymidine incorporation. Both LPS and TGF-beta 1 alone sti mulated EC expression of the adhesion molecules in a dose-dependent ma nner. The effects of TGF-beta 1 on LPS induction of the adhesion molec ules varied with LPS concentration and treatment time, mode, and durat ion. Pretreatment with TGF-beta 1 for 24 h greatly augmented LPS induc tion of ICAM-1 and VCAM-1 expression, but decreased E-selectin express ion. TGF-beta 1 also enhanced expression of the adhesion molecules in cells that were pretreated with 1 mu g/mL LPS for 60 min. Concomitant treatment with TGF-beta 1/LPS resulted in significant increases in ICA M-1 but decreases in VCAM-1 expression. TGF-beta 1 effects on LPS indu ction of the adhesion molecules were more prominent at lower LPS level s (.001, .01 mu g/mL). Both LPS and TGF-beta 1 suppressed thymidine in corporation in a dose-related pattern. These data suggest that TGF-bet a 1 has additive and antagonistic effects on LPS induction of the adhe sion molecules and that the cell responsiveness to the stimuli in the expression is related to growth condition of the cells. In conclusion, our findings suggest that TGF-beta 1 exhibits proinflammatory and ant i-inflammatory activities in human endothelial cells and may play an i mportant role in regulating leukocyte adherence and extravasation unde r LPS-induced inflammatory conditions.