The study demonstrates that thymosin α1 (Tα1) reduces cytokine production, normalizes signaling pathways, and suppresses cell apoptosis and the pro-inflammatory response. These findings highlight the potential of Tα1 as an anti-inflammatory agent in various diseases.

The aim of the study regarding thymosin α1 (Tα1) and RAW 264.7 macrophages is to investigate the effects of Tα1 on the pro-inflammatory response of the macrophages when they are exposed to lipopolysaccharide (LPS), which is derived from the walls of gram-negative bacteria. The study focuses on evaluating the production of pro-inflammatory cytokines, the activity of signaling pathways (NF-κB and SAPK/JNK), the expression of genes involved in cell apoptosis, and the activity of the TLR4 receptor. The goal is to assess the potential anti-inflammatory efficacy of Tα1 and its beneficial effects in various inflammatory conditions and diseases such as infectious diseases, cancer, immunodeficiency states, and neurological diseases.

The addition of Tα1 normalizes the production of pro-inflammatory cytokines in RAW 264.7 cells, particularly IL-1β and IL-6. It reduces the expression of TNF induced by lipopolysaccharide (LPS), which is used to model inflammation. Moreover, the presence of Tα1 in the cell culture medium significantly reduces the level of the pro-inflammatory response of the cells.

The research suggests that the presence of Tα1 in the cell culture medium reduces the activity of the NF-κB and SAPK/JNK signaling cascades, which are associated with cell activity in the presence of damaging agents. The addition of Tα1 normalizes the activity of these signaling pathways and protects cells from the damaging effects of endotoxin. The activation of the SAPK/JNK cascade induced by endotoxin is eliminated in the presence of Tα1. Tα1 also normalizes the expression of the Nf-κb gene, which is involved in the NF-κB signaling pathway. Therefore, Tα1 has a significant impact on reducing the activity of NF-κB and SAPK/JNK signaling pathways.

Tα1 has a significant effect on the expression of genes related to cell apoptosis. The presence of Tα1 in the cell culture medium reduces the expression of the p53 gene, which regulates the level of cell apoptosis, under the influence of endotoxin. It also significantly reduces the activity of the P53 gene, a marker of cell apoptosis, in the presence of LPS. Moreover, the addition of Tα1 normalizes the expression of all the studied genes related to cell apoptosis, except for the inos gene, which encoding inducible NO-synthase, and its synthesis increases by 13 times in the presence of Tα1. Overall, Tα1 demonstrates a regulatory effect on genes involved in cell apoptosis, effectively reducing their expression levels.

The overall effect of Tα1 on the pro-inflammatory response of RAW 264.7 cells is that it significantly reduces the level of the pro-inflammatory response. The addition of Tα1 normalizes the production of pro-inflammatory cytokines, particularly IL-1β and IL-6, and reduces the activity of the NF-κB and SAPK/JNK signaling pathways. It also decreases the expression of the p53 gene, a marker of cell apoptosis, and reduces the expression of the Ar-1 gene under the influence of endotoxin. Additionally, the presence of Tα1 in the cell culture medium stimulates cell viability and has no toxic effects. Overall, Tα1 demonstrates an anti-inflammatory efficacy and potential beneficial effects in various diseases, including infectious diseases, cancer, immunodeficiency states, and neurological diseases.

Full article can be found here: https://doi.org/10.1134/S0026893323060110