Tumor Necrosis Factor a/TNFa Protein(N-6His) (recombinant human)

Activity: Measured in a cytotoxicity assay using L-929 mouse fibroblast cells in the presence of the metabolic inhibitor actinomycin D. The ED50 for this effect is less than 1 ng/ml. Protein Construction: Recombinant Human Tumor Necrosis Factor alpha is produced by our E.coli expression system and the target gene encoding Gly57-Leu233 is expressed with a 6His tag at the N-terminus. Sequence: Gly57-Leu233. Fusion tag: N-6His Endotoxin: < 1.0 EU per µg as determined by the LAL method. Apparent Molecular Mass: 21 kDa. Protein function: Tumor Necrosis Factor-a (TNF-a) is secreted by macrophages, monocytes, neutrophils, T-cells, and NK-cells following stimulation by bacterial LPS. Cells expressing CD4 secrete TNF-a while cells that express CD8 secrete little or no TNF-a. Synthesis of TNF-a can be induced by many different stimuli including interferons, IL2, and GM-CSF. The clinical use of the potent anti-tumor activity of TNF-a has been limited by the proinflammatory side effects such as fever, dose-limiting hypotension, hepatotoxicity, intravascular thrombosis, and hemorrhage. Designing clinically applicable TNF-a mutants with low systemic toxicity has been of intense pharmacological interest. Human TNF-a that binds to murine TNF-R55 but not murine TNF-R7, exhibits retained anti-tumor activity and reduced systemic toxicity in mice compared with murine TNF-a, which binds to both murine TNF receptors. Based on these results, many TNF-a mutants that selectively bind to TNF-R55 have been designed. These mutants displayed cytotoxic activities on Protein function: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918, PubMed:16829952, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance. [The UniProt Consortium]