Thymosin α1 interacts with Galectin-1 modulating the β-galactosides affinity and inducing alteration in the biological activity

The study of mechanism of action of Thymosin alpha 1 (T alpha 1) and the basis of the pleiotropic effect in health and disease, is one of the main focus of our ongoing research. T alpha 1 is a thymic peptide that demonstrates a peculiar ability to restore homeostasis in different physiological and pathological conditions (i.e., infections, cancer, immunodeficiency, vaccination, and aging) acting as multitasking protein depending on the host state of inflammation or immune dysfunction. However, few are the information about mechanisms of action mediated by specific T alpha 1-target protein interaction that could explain its pleiotropic effect. We investigated the interaction of T alpha 1 with Galectin-1 (Gal-1), a protein belonging to an oligosaccharide binding protein family involved in a variety of biological and pathological processes, including immunoregulation, infections, cancer progression and aggressiveness. Using molecular and cellular methodological approaches, we demonstrated the interaction be-tween these two proteins. T alpha 1 specifically inhibited the hemagglutination activity of Gal-1, the Gal-1 dependent in vitro formation of endothelial cell tubular structures, and the migration of cancer cells in wound healing assay. Physico-chemical methods revealed the details of the molecular interaction of T alpha 1 with Gal-1. Hence, the study allowed the identification of the not known until now specific interaction between T alpha 1 and Gal-1, and unraveled a novel mechanism of action of T alpha 1 that could support understanding of its pleiotropic activity.