Recombinant Human TNF-alpha

Tumor necrosis factor alpha (TNF-alpha), is a pleiotropic pro-inflammatory cytokine secreted by various cells, including adipocytes, activated monocytes, macrophages, B cells, T cells and fibroblasts ^{[1, 2]}. It belongs to TNF family of ligands, and signals through two receptors, TNFR1 and TNFR2. Human TNF-alpha consisits of a 35 amino acid (aa) cytoplasmic domain, a 21 aa transmembrane segment, and a 177 aa extracellular domain (ECD) ^[3]. The ECD of human TNF-alpha shares 97% aa sequence identity with rhesus and 71%-92% with bovine, canine, cotton rat, equine, feline, mouse, porcine, and rat TNF-alpha. TNF-alpha is assembled intracellularly to form a noncovalently linked homotrimer which is expressed on the cell surface ^[4]. Cell surface TNF-alpha can induce the lysis of neighboring tumor cells and virus infected cells, and it can generate its own downstream cell signaling following ligation by soluble TNFR1 ^{[2, 5]}. Shedding of membrane bound TNF-alpha by TACE/ADAM17 releases the bioactive cytokine, a 55 kDa soluble trimer of the TNF-alpha extracellular domain ^[6-8]. TNF-alpha binds the ubiquitous 55-60 kDa TNFR1^{[9, 10]} and the hematopoietic cell-restricted 80 kDa TNFR2 ^{[11, 12]}, both of which are also expressed as homotrimers ^{[1, 2, 13]}.

Reference

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[3]. Pennica, D. et al. (1984) Nature 312:724.

[4]. Tang, P. et al. (1996) Biochemistry 35:8216.

[5]. Perez, C. et al. (1990) Cell 63:251.

[6]. Black, R.A. et al. (1997) Nature 385:729.

[7]. Moss, M.L. et al. (1997) Nature 385:733.

[8]. Gearing, A.J.H. et al. (1994) Nature 370:555.

[9]. Schall, T.J. et al. (1990) Cell 61:361.

[10]. Loetscher, H. et al. (1990) Cell 61:351.

[11]. Dembic, Z. et al. (1990) Cytokine 2:231.

[12]. Smith, C.A. et al. (1990) Science 248:1019.

[13]. Loetscher, H. et al. (1991) J. Biol. Chem. 266:18324.