Involvement of phosphatidylinositol-3 kinase-Akt and nuclear factor kappa-B pathways in the effect of frutalin on human lymphocyte.

The mechanisms involved in the mitogenic effect of lectins are not fully understood and are thought to involve a cascade of intracellular signals related to T cell receptor activation. This study shows that frutalin, the alpha-D-galactose-binding lectin from Artocarpus incisa seeds, is a potent mitogenic activator of human lymphocytes. This effect is inhibited by D-galactose and PI3K inhibitors, and is accompanied by an increase in IL-2 receptor expression and by a PI3K-dependent IL-2 gene expression and IL-2 protein synthesis. Frutalin also induces Akt-phosphorylation and activates NF-kappaB, inducing its translocation from the cytosol to the nucleus. Both effects are blocked in the presence of D-galactose or by PI3K inhibitors. In summary, frutalin, interacting with alpha-D-galactose, activates signaling pathways related to TCR, and thereby triggers PI3K/Akt and NF-kappaB pathway, which modulates T cell proliferation, IL-2 synthesis and IL-2R expression. Frutalin might be a useful tool to study intracellular mechanisms following T cell activation that link upstream signaling pathways to downstream events.