The Effect of Drugs with α-Glutamyl–Tryptophan for Cytokine Secretion and Level of Surface Molecule ICAM-1 In Vitro

• Published in: Cell and tissue biology 2023, Vol.17 (2), p.146-152
• Main Authors: Golovacheva, E. G., Starikova, E. A., Kudryavtseva, T. A., Apryatina, V. A.
• Format: Article
• Language: English
• Subjects: Anti-inflammatory agents; Biomedical and Life Sciences; Cell Biology; Cell culture; Cytokines; Endothelial cells; Immune response; Immunomodulation; Immunosuppressive agents; Inflammation; Intercellular adhesion molecule 1; Interleukin 8; Leukocytes (mononuclear); Life Sciences; Molecular modelling; Peripheral blood mononuclear cells; Tryptophan; Tumor necrosis factor-α
• ISSN: 1990-519X; 1990-5203
• DOI: 10.1134/S1990519X23020050

The study of the molecular mechanisms underlying the action of immunomodulatory drugs is important for substantiating their therapeutic effect. In the present work, spontaneous and TNFα-induced secretion of IL-1α and IL-8 pro-inflammatory cytokines, as well as the level of the ICAM-1 adhesion molecule in EA.hy 926 endothelial cell culture and peripheral blood mononuclear cells of healthy donors, is studied using an in vitro model of inflammation in the presence of α-glutamyl–tryptophan (α-Glu–Trp) and Cytovir-3. The aim was to evaluate cellular mechanisms mediating the immunomodulatory effect of α-Glu–Trp and Cytovir-3 drugs. It was shown that α-Glu–Trp reduced TNFα-induced IL-1α production and increased TNFα-stimulated level of the ICAM-1 surface molecule of endothelial cells. At the same time, the drug reduced secretion of the IL-8 cytokine induced by TNFα and increased the spontaneous level of ICAM-1 in mononuclear cells. Cytovir-3 had an activating effect on EA.hy 926 endothelial cells and human peripheral blood mononuclear leukocytes. In its presence, there was an increase in the spontaneous secretion of IL-8 by endothelial and mononuclear cells. In addition, Cytovir-3 increased the level of TNFα-induced ICAM-1 on endothelial cells and increased the spontaneous level of this surface molecule on mononuclear cells. Suppression of stimulated production of pro-inflammatory cytokines under the action of α-Glu–Trp both separately and as a part of Cytovir-3 may determine its anti-inflammatory properties. However, an increased level of the surface ICAM-1 molecule indicates mechanisms that enhance the functional activity of these cells, which is equally important for the implementation of an effective immune response to infection and repair of damaged tissues during inflammatory response.