Tumor Necrosis Factor (TNF) Superfamily

By: Jennifer Fries, BioFiles 2009, 4.5, 23.

BioFiles 2009, 4.5, 23.

The tumor necrosis factor (TNF) superfamily comprise an increasing number of structurally related ligand-receptor pairs, including TNF-α, TNF-β (lymphotoxin, LT), TNFR1, TNFR2, LT-βR, osteoprotegrin (OPG), RANK, RANKL (TRANCE), TRAIL (APO-2L), DR4 (TRAIL-R1), DR5 (TRAIL-R2), DcR1 (decoy receptor 1, TRAIL-R3), and DcR2 (decoy receptor 2, TRAIL-R4). Except for one member, all receptors to the TNF superfamily bind TNF-related ligands and act mainly on the immune system. The exception is p75NGF, distinctly homologous to TNF receptors, but which binds neurotrophins (NGF, BDNF, NT-3 and NT-4) and exerts its actions on the nervous system. (See Neurotrophic Factors section for this receptor description.)

Although a variety of actions are reported for the TNF superfamily, a common theme is their ability to regulate cell viability. They play important roles in lymphoid development and in T and B cell responses. Several TNF superfamily receptors induce apoptosis, but many TNF members may also induce lymphocyte proliferation and differentiation through costimulation with antigen receptors. TNF superfamily ligands (except neurotrophins) share several common features. Synthesized as a type II transmembrane protein (extracellular C-terminus) without secretion signal sequence, these ligands are usually released from the outer cell membrane by proteolytic cleavage, except for TNF-β (lymphotoxin, LT or LT-α) which has a nonfunctional transmembrane section and so is secreted from the cell directly. TNF superfamily members are usually long-chain β-sheet “jellyroll’’ cytokines that form coneshaped homotrimers in solution. The surface form of lymphotoxin is unusual, as it is a heterotrimer containing one or two molecules of the membrane-attached LT-β with one or two LT-α (TNF-β) chains, with LT-α1LT-β2 as the predominant form.


Hetrokaryons between proliferating (BrdU pre-labeled) and quiescent (unlabeled) endothelial cells were treated with TNF-α to induce programmed cell death (apoptosis). BrdU incorporation into DNA was detected with Monoclonal Anti-BrdU, (clone no. BU-33, Cat. No. B2531) followed by goat Anti-Mouse IgG-β-galactosidase. After staining with acridine orange (Cat. No. A6014) cells were visualized by phase contrast (left) and fluorescent (right) microscopy. Tailed arrows indicate intact (solid) or apoptotic (dotted) BrdU positive nuclei, arrow heads point to normal (solid) and apoptotic (notched) BrdU negative nuclei. 

From V. Polunovsky, Univ. of Minnesota, Minneapolis, MN.

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Tumor Necrosis Factor-α (TNF-α)

Product Description Source Recombinant Host Physical Form Assay Cell Type Affected Cat. No.
Tumor Necrosis Factor-α human yeast buffered aqueous solution - osteoclast human fibroblast PMN cell T0157-10UG
Tumor Necrosis Factor-α from rat Escherichia coli powder The biological activity is measured in a cytotoxic assay using a TNF-susceptible mouse L929 cell line in the presence of actinomycin D. PMN cell human fibroblast osteoclast T5944-10UG
Tumor Necrosis Factor-α from mouse Escherichia coli powder - human fibroblast osteoclast PMN cell T7539-10UG
Tumor Necrosis Factor-α human Escherichia coli powder The biological activity of TNF-α is measured by the cytolysis of murine L929 cells. PMN cell osteoclast human fibroblast T6674-10UG

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Tumor Necrosis Factor-β (TNF-β)

Product Description Source Recombinant Host Physical Form Assay Cell Type Affected Cat. No.
Tumor Necrosis Factor-β human Escherichia coli powder The biological activity is measured in a cytotoxicity assay using the TNF-suspectible murine L929 cell line in the presence of actinomycin D. PMN cell human fibroblast osteoclast T7799-10UG

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Materials

     

References

  1. Ware, C., et al., Tumor necrosis factor-related ligands and receptors, in The Cytokine Handbook, 3rd Edition, Thomson, A.W., ed., Academic Press (San Diego, CA: 1998), pp. 549-592.
  2. Gravestein, L., and Borst, J., T., Tumor necrosis factor family membersin the immune system. Sem. Immunol., 10, 423-434 (1998).

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