BIOCHEMICAL EFFECTS OF TLRs, CXCL12, AND NECROSOME ACTIVATION ON PRO-B LYMPHOCYTE APOPTOSIS IN THE PRESENCE OF FIBROBLASTS

Abstract

Aim of the study The accelerated development of the tumor mass in acute lymphoblastic leukemia depends not only on the proliferative rate of cells but also on the rate of apoptosis, with NR4A1 dually controlling both the survival and death of tumoral cells. Material and methods The experimental plan of the actual studies was represented by highlighting the effects of the activation of the NR4A1 orphan receptor, in the presence of exosomes released from gingival fibroblasts, on the apoptosis of tumor precursors of B lymphocytes, pro-B respectively, and also in the presence of toll-like receptors, CXCL12, and necrosome modulators. Results The obtained results demonstrate that between the apoptosis induced by cytosporone B in the case of exosomes+ pro-B cells, after 48 hours of diverse treatments, and the control cells, there are statistically significant differences (the averages being comparatively 71.84% for 1 µM lipopolysaccharide; 91.25% for 1 µM AMG9810; 63.14% for 1 µM necrostatin 2 racemate; 61.77% for 1 µM tannic acid; and, respectively, 10% for control ones). Conclusions The most important effects of enhancing apoptosis induced by cytosporone B in the presence of exosomes released from gingival fibroblasts were under the following treatments: lipopolysaccharide in chronic conditions; inhibition of the functioning of TLR4 receptors; reduction of RNA for the toll-like receptors TLR4 and TLR2; and inhibition of the CXCL12 pathway. Thus, it is demonstrated that the exosomes of the tumoral microenvironment (gingival fibroblasts in this case) greatly influence the development of tumoral cells, in balance with apoptosis.

Keywords

• pro-b lymphocyte
• apoptosis
• fibroblast
• exosomes
• tlr
• cxcl12
• necrosome