ROOPEROL TETRAACETATE DECREASES CYTOKINE MESSENGER-RNA LEVELS AND BINDING-CAPACITY OF TRANSCRIPTION FACTORS IN U937 CELLS

WE have previously described inhibition of the synthesis of three acut e-phase inflammatory cytokines in human and rat macrophages by acetate esters of rooperol, a dicatechol of plant origin. Analysing the mecha nism of anticytokine activity of rooperol, we compared levels of TNF a lpha, IL-1 beta and IL-6 mRNAs in the human promonocytic U937 cell lin e pretreated with phorbol myristate acetate (PMA) and incubated with r ooperol tetraacetate (RTA) alone or in combination with LPS (500 ng/ml ). It was found that 10 mu M RTA decreased the levels of cytokine mRNA s both in the presence and absence of LPS, suggesting pretranslational inhibition of cytokine synthesis. Electrophoretic mobility shift anal ysis (EMSA) showed that RTA may influence cytokine mRNA expression by decreasing the binding activity of transcription factors NF-kappa B an d AP-1.