Ellagic Acid, a Dietary Polyphenol, Inhibits Tautomerase Activity of Human Macrophage Migration Inhibitory Factor and Its Pro-inflammatory Responses in Human Peripheral Blood Mononuclear Cells

Ellagic acid (EA), a phenolic lactone, inhibited tautomerase activity of human macrophage migration inhibitory factor (MLF) noncompetitively (K-i = 1.97 +/- 0.7 mu M). The binding of EA to MIF was determined by following the quenching Of tryptophan fluorescence. We synthesized several EA derivatives, and their structure activity relationship studies indicated that the planar conjugated lactone moiety of EA was essential for MLF inhibition. MIF induces nuclear translocation of NF-kappa B and chemotaxis of peripheral blood mononuclear cells (PBMCs) to promote inflammation. We were interested in evaluating the effect of EA on nuclear translocation of NF-kappa B and chemotactic activity in human PBMCs in the presence Of MIF. The results showed that EA inhibited MIF-induced NF-kappa B nuclear translocation in PBMCs, as evident from confocal immunofluorescence microscopic data. EA also inhibited MIF-mediated chemotaxis of PBMCs. Thus, we report MIF-inhibitory activity of EA and inhibition of MIF-mediated proinflammatory responses in PBMCs by EA.