Recombinant Human Tumor Necrosis Factor a/TNFa (C-6His)

Source: E. coli. MW :18.5kD. Recombinant Human Tumor Necrosis Factor alpha is produced by our E.coli expression system and the target gene encoding Val77-Leu233 is expressed with a 6His tag at the C-terminus. 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 tumor cell lines in vitro and have exhibited lower systemic toxicity in vivo. Recombinant Human TNF-a High Active Mutant differs from the wild-type by amino acid subsitution of amino acids 1-7 with Arg8, Lys9, Arg10 and Phe157. This mutant form has been shown to have increased activity with less inflammatory side effects in vivo. 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). [The UniProt Consortium]