Biomedical Engineering Reference
In-Depth Information
-sensitive genes by binding to a specifi c upstream regula-
tory sequence of the gene (the IFN-γ activated sequence, GAS). The PIAS-1 protein appears to
play an inhibitory role in this pathway. By complexing with (phosphorylated) STAT-1 proteins, it
inhibits DNA binding and transactivation.
nucleus. It regulates expression of IFN-
γ
8.2.8 The biological effects of interferons
Interferons induce a wide range of biological effects. Generally, type I interferons induce similar
effects, which are distinct from the effects induced by IFN-
. The most pronounced effect of type I
interferons relates to their antiviral activity, as well as their anti-proliferative effect on various cell
types, including certain tumour cell types. Anti-tumour effects are likely due not only to a direct
anti-proliferative effect on the tumour cells themselves, but also due to the ability of type I interferons
to increase NK and T-cytotoxic cell activity. These cells can recognize and destroy cancer cells.
Not all type I interferons induce exactly the same range of responses, and the antiviral to anti-
proliferative activity ratio differs from one type I interferon to another. As all bind the same recep-
tor, the molecular basis by which variation in biological activities is achieved is poorly understood
as yet.
IFN-γ exhibits, at best, weak antiviral and anti-proliferative activity. When co-administered
with type I interferons, however, it potentates these IFN-
γ
is directly involved
in regulating most aspects of the immune and infl ammatory responses. It promotes activation,
growth and differentiation of a wide variety of cell types involved in these physiological processes
(Table 8.7).
IFN-
α
/
β
activities. IFN-
γ
represents the main macrophage-activating factor, thus enhancing macrophage-mediated
effects, including:
γ
•
destruction of invading microorganisms;
•
destruction of intracellular pathogens;
•
tumour cell cytotoxicity;
•
increased major histocompatibility complex (MHC) antigen expression, leading to enhanced
activation of lymphocytes via antigen presentation.
Table 8.7
Cell types participating in the immune, infl ammatory or other
responses whose activation, growth and differentiation are promoted by IFN-
γ
Macrophages/monocytes
Polymorphonuclear neutrophils
T-lymphocy tes
B-lymphocytes
NK cells
Fibroblasts
Endothelial cells
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