Features of changes in the expression level of TNFα receptors and the functional response of cell lines upon stimulation with various doses of cytokine

Abstract

TNFa is a pro-inflammatory cytokine that is signaled through type 1 (TNFR1) and type 2 (TNFR2) receptors. TNFR1 normally mediates apoptosis, cell survival, and cytokine secretion, while TNFR2 selectively mediates cell survival and cytokine secretion. But in some cases, when receptors are activated, the functional response of cells changes to the opposite. Activation of signaling pathways has its own triggers, which differ in the interaction between different forms of cytokine and different forms of receptor complexes, as well as changes in the ratio of different types of receptors. The study of the mechanisms of regulation in the ligand-receptor system is a priority task for many studies. This work shows the dose-dependent effect of TNFa on the expression of cytokine receptors and changes in the functional response of tumor cell lines of various origins. For this, a comparative assessment of the expression and co-expression of receptors, cell cycle phases and apoptosis of cell lines without stimulation and stimulated with TNFa at concentrations of 5 and 50 ng/mL was carried out. It was found that the K562 cell line was characterized by more pronounced changes in receptor co-expression, which were observed at a TNFa concentration of 50 ng/mL compared to both the control group and the 5 ng/mL group. The decrease in the relative content of cells expressing only TNFR1 was combined with a decrease in the percentage of cells in apoptosis, which confirms the literature data on the role of this receptor in the development of apoptosis. At the same time, no changes in expression density were observed for this cell line. For the ZR75-1 cell line, the largest number of effects was also found for a TNFa concentration of 50 ng/mL. An increase in the relative content of cells expressing only TNFR2 was combined with an increase in apoptosis; however, the expression density of this type of receptor was low, which could affect the switching of signaling pathways towards proapoptotic ones. Thus, our study allowed us to reveal the features of changes in the expression and co-expression of TNFa receptors characteristic of cell lines of various origins, as well as changes in the functional response of cells in response to stimulation with different doses of cytokine. All this allows us to expand our understanding of the regulatory mechanisms in the cytokine-receptor system.