THE EFFECT OF THYMOSIN β4 ON THE FUNCTIONAL ACTIVITY OF THE IMMUNE AND NERVOUS SYSTEM COMPONENTS

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Introduction. Pathogenesis of many infectious and autoimmune diseases as well as neurodegenerative disorders is related to the functional disbalance of basic cells in both systems. To correct the immune and neuronal status, changed or damaged during various pathological processes, the natural double-duty peptide preparations regulating functions both immunocompetent and neuronal cells can be used. Among such agents is thymosin β4. Structure and functions of thymosin β4. Thymosin β4 (Figure 1) is a member of a family consisting of highly conserved polypeptides, primarily isolated from thymus and characterized as a compound regulating the maturation and differentiation processes of T cells [2]. Thymosin β4 is the most abundant β-thymosins both in the immune and nervous systems of mammals. Thymosin β4 realizes numerous different functions including its participation in the regulation of the immune and nervous system activity (Table 1) [2, 5]. It has been observed that thymosin β4 regulates functions of various cells such as lymphocytes, neutrophils, macrophages, mast cells (immune system); neurons, astrocytes, oligodendrocytes, microglial cells (nervous system). Wherein, thymosin β4 affects activity both stationary and migratory cells, changing biochemical and morphological characteristics of cells. Thymosin β4: structural-functional relationships. The data accumulated indicates that peptide fragments of thymosin β4 may exhibit biological activity. N-terminal tetrapeptide Ac-SDKP, representing the fragment 1-4 of thymosin β4, inhibits the proliferation of lymphocytes, as well as pluripotent hematopoietic stem cells, induces the degranulation of mast cells, inhibits a collagen synthesis by fibroblasts and reduces the TGFβ activity. This tetrapeptide has been shown to be generated by a prolyl-oligopeptidase [7]. The pentapeptide fragment 10-14 of thymosin β4, EKFDK, has immunoregulatory activity. The pentapeptide has been shown to stimulate the mitogen-induced proliferative response of human T-lymphocytes, as well as antibody genesis at the secondary immune response to T-dependent antigen in mice [3]. Besides, this peptide influences functions of phagocytic cells in particular it stimulates migration and oxidative metabolism of human granulocytes [4]. The main function of the hexapeptide fragment 17-22 of thymosin β4, LKKTET, is a primarily binding with actin monomers. The heptapeptide 17-23 of thymosin β4, isolated from wound fluid, regulates mast cell functions inducing exocytosis of compounds normalizing the wound healing processes [7]. In human T-lymphocytes the thymosin β4 fragments 16-26 and 31-39 induce expression of CD2 antigens which are important for the acceleration of adhesion between T-lymphocytes and other immunocompetent cells [1]. It is wide-spread opinion that the intracellular functions of thymosin β4 are connected with its ability to regulate the processes of actin polymerization through G-actin monomer sequestration. Binding with G-actin, thymosin β4 prevents actin filament formation [6]. However, there are reports concerning the participation of thymosin β4 in physiological events, not connected with sequestration of actin, such as inflammation, apoptosis, angiogenesis and wound healing. In some cases the extracellular location of thymosin β4 has been revealed although pathways of thymosin β4 releasing from cells are still not discovered. It remains unclear, what kinds of cell surface receptors participate in mediating of thymosin β4 functions. It should be noted that thymosin β4 has great therapeutic potential. Thymosin β4 and its peptide fragments could be useful for the therapy of diseases related to immune dysfunctions and neurological disturbances. The research was carried out within the state assignment of FASO of Russia (theme No. АААА-А18-118012290371-3).

About the authors

V P Ivanova

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Saint Petersburg

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