TNF-binding protein

Tumor necrosis factor a (TNF-a) is a multifunctional cytokine produced by activated monocytes-macrophages. TNF-a is one of the most potent osteoclastogenic cytokines produced in inflammation, and, in addition, TNF-a induces IL-1 synthesis. Like the other known stimulators of bone resorption, it acts through osteoblastic cells however, it has been demonstrated that TNF-a is able to induce osteoclast formation from stromal-depleted macrophages, with potency similar to that of RANKL (Kobayashi et al. 2000). TNF-a is able to induce bone resorption in vitro (Thomson et al. 1987) as well as in vivo (Koning et al. 1988). Osteoclasts induced by TNF-a have the capacity to form resorption pits on dentine slices only in the presence of IL-la. TNF-a, together with IL-1, plays an important role in bone resorption in inflammatory diseases (Kobayashi et al. 2000). Inhibition of TNF by TNF binding protein (TNFbp) completely prevents bone loss and osteoclast formation (Kimble et al. 1997). 

Kapadia, S., Torre-Amione, G., Yokoyama, T., and Mann, D. L. (1995). Soluble TNF binding proteins modulate the negative inotropic properties of TNF-alpha in vitro. Am. J. Physiol. 268, H517-HS25. 

G22. Gray, P. W., Barrett, K Chantry, D., Turner, M., and Feldmann, M. Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression of recombinant soluble TNF-binding protein. Proc. Natl. Acad. Sci. U.SA. 87, 7380-7384 (1990). 

Soluble fragments of TNF-Rs were first referred to as TNF-binding proteins, having been discovered in the biological fluids of health volunteers, postmenopausal women, and patients with cancer or chronic renal disease (Olsson et al., 1993). These soluble forms of TNF-Rs are immunologically distinct from one another but demonstrate functional cross-reactivity with the surface receptors (Engelmann et al., 1990b). 

The discovery of these soluble TNF-R fragments has preceded the understanding of how they are generated. Since molecular studies have not been able to identify mRNA specific for the soluble TNF-R forms, and amino acid sequences of the soluble forms are identical to those of the extracellular domains of surface TNF-Rs (Nophar et al., 1990), it has been concluded that the fragments are released from the cleavage of surface receptors and are not produced from alternatively spliced surface TNF-R transcripts. Additional supporting evidence for this conclusion is that TNF-binding proteins... 

Olsson, L, Gatanaga, T., Gullberg, U., Lantz, M., and Granger, G. A. (1993). Tumor necrosis factor (TNF) binding proteins (soluble TNF receptor forms) with possible roles in inflammation and malignancy. Eur. Cytokine Network 4, 169-180. 

TNF-binding protein 1 TNF-binding protein 2 Transcobalamin Transcortin Transferrin... 

So far, poxviruses are the oidy viruses that express viral modulators that can bind and sequester extracellukr TNF prior to its TNFR engagement. Two distinct classes of extracellular poxvirus TNF-binding proteins have been identified those that resemble the manunalian TNFRs, termed vTNFRs and a recendy characterized fiunily of proteins that resemble the manunalian MHC class I heavy chain, termed vTNF-BPs, that bind and inhibit TNF with unusually tight affinity. ... 

Viral TNF-Binding Proteins Unrelated to Host TNFRs... 

Gileva IP, Nepomnyashchikh TS, Antonets DV et al. Properties of the recombinant TNF-binding proteins from variola, monkeypox and cowpox viruses are different. Biochim Biophys Acta 2006 1764(11) 1710-1718. 

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