TNF-ALPHA INDUCES DYSCOHESION OF EPITHELIAL-CELLS - ASSOCIATION WITH DISASSEMBLY OF ACTIN-FILAMENTS

TNF-alpha induced, in a time and dose-dependent fashion, cell-cell dis sociation (dyscohesion) of endometrial epithelial cells. Within the ti me frame that dyscohesion was induced, TNF-alpha, in a dose-dependent fashion, reduced filamentous (F) actin and resulted in the loss of F-a ctin from the intercellular boundaries. Loss of F-actin mediated by TN F-alpha was not due to a reduction in the overall amount of actin or i ts beta-isoform. Two proteins, Rho and Rho guanine nucleotide dissocia tion inhibitor (Rho-GDI), have been implicated in the regulation of or ganization of actin cytoskeleton. The reduced level of F-actin was not associated with altered expression of Rho protein, however, it was as sociated with an increase in the amount of Rho available for ribosylat ion in vitro by the C3 exoenzyme of Clostridium botulinum. The amount of Rho-GDI protein did not change after treatment with TNF-alpha sugge sting that elevated expression of this protein is not responsible for the disassembly of actin filaments. These findings show that TNF-alpha induces dyscohesion. Dyscohesion induced by this cytokine is associat ed with perturbation of the actin cytoskeleton which may be due to the regulatory role of TNF-alpha on Rho.