Biomedical Engineering Reference
In-Depth Information
Figure 9.4 Three-dimensional structure of TNF- α . Structural details courtesy of the Protein Data Bank,
http://www.rcsb.org/pdb/
upon their activation. After activation, the rate of gene expression may increase only threefold,
although cellular TNF-
α
mRNA levels may increase 100-fold and secretion of soluble TNF-
α
may increase 10 000-fold.
9.5.2 Biological activities of tumour necrosis factor- α
The availability of large quantities of recombinant TNF-
facilitates rigorous investigation of the
effects of this cytokine on cells in vitro , as well as its systemic in vivo effects. Like most cytokines,
TNF-
α
exhibits pleiotropic effects on various cell types. The major biological responses induced
by this cytokine include:
α
activation of certain elements of both non-specifi c and specifi c immunity, in particular in
response to Gram-negative bacteria;
Table 9.6 Major physiological inducers of TNF- α production
LPS
Mycobacteria
Fungi
Antibody-antigen complexes
Infl ammatory mediators
Bacterial enterotoxin
Various viruses
Parasites
Various cytokines (e.g. IL-1)
TNF-α (autocrine activity)
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