Soluble TNF-α (mouse, recombinant)

TNF-α is a cytokine and a member of the TNF/TNF receptor (TNFR) cytokine superfamily.¹ TNF-α is produced as a 233-amino acid transmembrane precursor protein from which mature, soluble TNF-α is formed by proteolysis.² Soluble TNF-α is a 157-amino acid polypeptide, cleaved from the precursor protein on the extracellular side of the membrane, that forms bell-shaped homotrimers with the C-termini at the base, each containing three receptor interaction sites.³ It is primarily produced by activated macrophages but can also be produced by a variety of other cells, such as T cells, natural killer cells, and osteoblasts.^3,4 TNF-α binds to and activates its receptors, TNFR1 and TNFR2, which are associated with intracellular protein complexes that activate caspases to induce cell death, induce p38 MAPK signaling, and initiate NF-κB or AP-1-mediated transcription of immune and inflammatory mediators.⁵ TNF-α promotes inflammation partly by inducing endothelial cells to express adhesion molecules, COX enzymes, and pro-coagulant factors.⁴ Exogenous TNF-α induces death of cancer cells in vitro, as well as disrupts tumor vascularization and induces necrosis in vivo, but it has tumor promoting properties when produced in the cancer microenvironment.^6,1 In contrast, it plays a role in resistance to infection, with mice lacking Tnf having an increased susceptibility to certain microbial infections but lacking resistance to leishmania.⁵ Tnf knockout mice are also resistant to certain types of cancer, including chemically induced skin carcinogenesis.¹ TNF-α increases lung metastases in a mouse model of fibrosarcoma, an effect that can be reduced by an anti-TNF-α antibody. Mice overexpressing Tnf develop an arthritis similar to rheumatoid arthritis in humans.⁷ TNF-α is produced in the inflamed tissues of patients with inflammatory diseases such as rheumatoid arthritis, and neutralizing antibodies to TNF-α reduce the levels of TNF-α in vitro and in mouse models of the disease.⁴ Cayman’s Soluble TNF-α (mouse, recombinant) protein can be used for cell-based assay applications. This protein consists of 157 amino acids and has a calculated molecular weight of 17 kDa.

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1. Balkwill, F. TNF-α in promotion and progression of cancer. Cancer Metastasis Rev. 25(3), 409-416 (2006).

2. Kriegler, M., Perez, C., DeFray, K., et al. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: Ramifications for the complex physiology of TNF. Cell 53(1), 45-53 (1988).

3. Tang, P., Hung, M., and Klostergaard, J. Human pro-tumor necrosis factor is a homotrimer. Biochemistry 35(25), 8216-8225 (1996).

4. Bradley, J.R. TNF-mediated inflammatory disease. J. Pathol. 214(2), 149-160 (2008).

5. Idriss, H.T., and Naismith, J.H. TNFα and the TNF receptor superfamily: Structure-function relationship(s). Microsc. Res. Tech. 50(3), 184-195 (2000).

6. Josephs, S.F., Ichim, T.E., Prince, S.M., et al. Unleashing endogenous TNF-alpha as a cancer immunotherapeutic. J. Transl. Med. 16(1), 242 (2018).

7. Li, P., and Schwarz, E.M. The TNF-α transgenic mouse model of inflammatory arthritis. Springer Semin. Immunopathol. 25(1), 19-33 (2003).