Apoptosis of pro-B lymphocytes induced by NR4A1 activation in the presence of gingival fibroblast exosomes and TNFalpha, caspase 8, STAT3, and Akt pathways modulators

Vol. 64 No. 1, 2023


Carmen Amititeloaie, Liliana Chelaru, Gabriela Luminita Geletu, Anca Sava, Alexandra Jitareanu, Andreea Mihaela Tibeica, Marcel Costuleanu

There is a lack of data in the mainstream literature regarding the interactions between gingival fibroblasts, as a component of the local niche, and tumor precursors of B-lymphocytes. Although it is known that the development of tumors and tumor precursors depends on the local environment s characteristics. In order to experimentally evaluate the apoptosis of pro-B type lymphocytes, induced as a result of the known activation of orphan nuclear receptor 4A1 (NR4A1), through Cytosporone B (Csn-B, 10 micro-M), in the presence or absence of exosomes derived from gingival fibroblasts, we administered as a treatment: 1 micro-M R-7050 [functional inhibitor of tumor necrosis factor alpha (TNFalpha)], 1 micro-M Z-IETD-FMK (functional inhibitor of caspase 8), 1 micro-M GSK690693 (functional inhibitor of Akt 1/2/3 pathways) and, last but not least, 1 micro-M scutellarin [functional inhibitor of receptor activator of nuclear factor-kappa B ligand (RANKL)] and therefore of the signal transducer and activator of transcription 3 (STAT3) pathway. Firstly, it is really clear that the presence of exosomes in the pro-B lymphocytes culture medium amplified the apoptotic effects of 10 micro-M Csn-B. The inhibition of tumoral precursors development, namely the pro-B type, might be highly dependent on the inhibition of Akt 1/2/3 pathways, the first and most important consequence being apoptosis induced by the activation of NR4A1 orphan nuclear receptors.

Corresponding author: Liliana Chelaru, Lecturer, MD, PhD; e-mail: liliche_histo@yahoo.com; Gabriela Luminita Geletu, Lecturer, MD, PhD; e-mail: gabigeletu@yahoo.com

DOI: 10.47162/RJME.64.1.04 Download PDF
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