Melatonin and TGF-β-Mediated Release of Extracellular Vesicles.

Piekarska K; Bonowicz K; Grzanka A; Jaworski ŁM; Reiter RJ; Slominski AT; Steinbrink K; Kleszczyński K; Gagat M

Abstract

The immune system, unlike other systems, must be flexible and able to "adapt" to fully cope with lurking dangers. The transition from intracorporeal balance to homeostasis disruption is associated with activation of inflammatory signaling pathways, which causes modulation of the immunology response. Chemotactic cytokines, signaling molecules, and extracellular vesicles act as critical mediators of inflammation and participate in intercellular communication, conditioning the immune system's proper response. Among the well-known cytokines allowing for the development and proper functioning of the immune system by mediating cell survival and cell-death-inducing signaling, the tumor necrosis factor α (TNF-α) and transforming growth factor β (TGF-β) are noteworthy. The high bloodstream concentration of those pleiotropic cytokines can be characterized by anti- and pro-inflammatory activity, considering the powerful anti-inflammatory and anti-oxidative stress capabilities of TGF-β known from the literature. Together with the chemokines, the immune system response is also influenced by biologically active chemicals, such as melatonin. The enhanced cellular communication shows the relationship between the TGF-β signaling pathway and the extracellular vesicles (EVs) secreted under the influence of melatonin. This review outlines the findings on melatonin activity on TGF-β-dependent inflammatory response regulation in cell-to-cell communication leading to secretion of the different EV populations.