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| =='''Mechanism of action for IFNβ-1a'''== | | =='''Mechanism of action for IFNβ-1a'''== |
| IFNβis encoded by a single gene
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| with no introns (and hence, no splice variants), and no reported
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| polymorphisms. Although IFNβwas originally called fibroblast
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| IFN–because fibroblasts could be induced to produce it in vitro–
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| numerous other cell types can express IFNβ, including endothelial
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| cells, epithelial cells and various leukocytes. Unlike IFNα,
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| where a particular subset of dendritic cells appears to be one of the
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| primary in vivo sources, a physiological source of IFNβhas not
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| been identified. Endogenous IFNβis not generally detected at
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| significant levels in humans. So called “natural” human IFNβ
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| (expressed by fibroblasts in vitro), is glycosylated at one site with
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| an N-linked complex carbohydrate, the exact structure of which
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| can be influenced by growth conditions and the cell type
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| producing the IFN. While important for monomer stability,
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| solubility and, perhaps biodistribution, the carbohydrate moiety
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| does not appear to be required for receptor binding.
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|
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| '''The IFNβreceptor, signaling cascade and gene regulation''' | | '''The IFNβreceptor, signaling cascade and gene regulation''' |
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| signaling complexes in some cell types. | | signaling complexes in some cell types. |
| The current view of events leading to IFNβbiological activity is | | The current view of events leading to IFNβbiological activity is |
| as follows (Fig. 1A): 1) IFN binds to the extracellular domain of | | as follows: 1) IFN binds to the extracellular domain of |
| IFNAR2. 2) IFNAR1 then engages with the IFNβ–IFNAR2 complex, | | IFNAR2. 2) IFNAR1 then engages with the IFNβ–IFNAR2 complex, |
| forming the high-affinity receptor–ligand complex and allowing | | forming the high-affinity receptor–ligand complex and allowing |
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| resulting multifaceted biological response is in contrast to | | resulting multifaceted biological response is in contrast to |
| therapies such as monoclonal antibodies that have a much more | | therapies such as monoclonal antibodies that have a much more |
| specific molecular target. Thus, as shown inFig. 1B, IFNβmay exert | | specific molecular target[2-9]. |
| its therapeutic effects in two distinct ways: 1) direct effects of IFNβ
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| regulated gene products; or 2) indirect effects of IFN-regulated gene products, via effects on other genes (e.g. transcription
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| factors), or by altering populations or functions of cells including
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| Type 2 dendritic cells, monocytes, regulatory T-cells and CD56
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| bright NK cells[2-9].
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| [[Image:Mechanism of action of IFN.jpg]]
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| =='''Reference'''== | | =='''Reference'''== |
