Tumor necrosis factor (TNF) is a kind of cytokine, which is a small protein used by the immune system for cell signal transduction. Specifically, TNF signaling occurs through two receptors: TNFR1 and TNFR2. TNFR1 is constitutively expressed in most cell types. Besides, TNF2 is mainly in endothelial cells, epithelial cells, and immune cell subsets. Moreover, TNF1 signal transduction tends to promote inflammation and apoptosis. While TNFR2 signal transduction has an anti-inflammatory effect and promotes cell proliferation.
TNF-α is an inflammatory cytokine and is responsible for a diverse range of signaling events within cells, leading to necrosis or apoptosis. Furthermore, the protein is also important to fight infection and cancer. The main function of TNF is to regulate immune cells. Meanwhile, TNF is an immunostimulant in the treatment of some cancers. Nonetheless, anti-TNF drugs can treat various inflammatory diseases, such as rheumatoid arthritis. Here, we will introduce a potent TNF-α inhibitor, UTL-5g.
UTL-5g, a TNF-α Inhibitor, Possesses Chemoprotective and Liver Radioprotective Effects.
First of all, UTL-5g has chemoprotective and liver radioprotective effects. Importantly, UTL-5g lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by Cisplatin through TNF-α inhibition among other factors. Interestingly, UTL-5g is a chemoprotective agent, which can reduce the inflammation induced by chemotherapy, thus limiting the dose and duration of treatment.
In the second place, UTL-5g suppressed hyperphosphorylation of proteins involved in actin remodeling. Particularly, transcription factors that show a UTL-5g dose-dependent decrease in activity in two experiments are UTL-5g disruption.
Last but not the least, Pretreatment with UTL-5g disrupts actin remodeling-related pathways. Western blot analysis confirmed that UTL-5g destroyed LPS induced phosphorylation of ser5 of plastin-2. Obviously, UTL-5g pretreatment decreased STAT3 regulated transcriptional activity. At the same time, LPS stimulated JNK and its substrates Jun Ser73, Rptor Ser863, and Atf2 Thr53, but UTL-5g has no effect.
All in all, UTL-5g, a TNF-α inhibitor, possesses chemoprotective and liver radioprotective effects.
Carruthers NJ, et al. Eur J Pharmacol. 2017;811:66-73.