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IFN-beta

Beta-Interferon, abbr. bIFN.


ALTERNATIVE NAMES

Fibroblast interferon (Fi-IFN, F-IFN);
Type 1 interferon;
pH2-stable interferon;
R1-GI factor.
See also: individual entries for further information.


SOURCES

IFN-beta is produced mainly by fibroblasts and some epithelial cell types. The synthesis of IFN-beta can be induced by common inducers of interferons (see: IFN), including viruses, double-stranded RNA, and micro-organisms. It is induced also by some cytokines such as TNF and IL1.


PROTEIN CHARACTERISTICS

IFN-beta is a glycoprotein (approximately 20 % sugar moiety) of 20 kDa and has a length of 166 amino acids. Glycosylation is not required for biological activity in vitro.

The protein contains a disulfide bond Cys31/141) required for biological activity. At the DNA level IFN-beta displays 34 % sequence homology with IFN-beta-2 and approximately 30 % homology with other IFN-alpha subtypes. In contrast to IFN-gamma IFN-beta is stable at pH2.


GENE STRUCTURE

The human gene encoding IFN-beta has a length of 777 bp and maps to chromosome 9p22 in the vicinity of the IFN-alpha gene cluster. The IFN-beta gene does not contain introns. At least three different genes encoding IFN-beta have been found in the genomes of cattle.


RECEPTORS

IFN-beta binds to the same receptor as IFN-alpha.


BIOLOGICAL ACTIVITIES

In contrast to IFN-alpha IFN-beta is strictly species-specific. IFN-beta of other species is inactive in human cells.

IFN-beta is involved in the regulation of unspecific humoral immune responses and immune responses against viral infections. IFN-beta increases the expression of HLA class 1 antigens and blocks the expression of HLA class 2 antigens stimulated by IFN-gamma. IFN-beta stimulates the activity of NK-cells and hence also antibody-dependent cytotoxicity (see: ADCC). The activity of T suppressor cells elicited by several stimuli is stimulated also by IFN-beta. IFN-beta enhances the synthesis of the low affinity IgE receptor CD23. In activated monocytes (see also: cell activation) IFN-beta induces the synthesis of neopterin. It also enhances serum concentrations of Beta-2-Microglobulin. IFN-beta selectively inhibits the expression of some mitochondrial genes.

IFN-beta shows antiproliferative activity against a number of cell lines established from solid tumors.


TRANSGENIC ANIMALS, KNOCK-OUT, AND ANTISENSE STUDIES

An enhanced viral resistance and abnormalities in fertility are seen in transgenic mice expressing the human IFN-beta gene.


DETECTION AND ASSAY METHODS

Minute amounts of IFN-beta can be detected indirectly by measuring IFN induced proteins such as Mx protein. For further information see also subentry "Assays" in the reference section. Lewis describes a bioassay based on induction of a reporter gene linked to a promoter element that responds to interferons (see: IFN). Production of the reporter gene product is dose-dependent in the range of 1 to approximately 100 U/mL of IFN and sensitivity is comparable to standard cytopathic effect assays.

Mire-Sluis et al (1996) have described bioassays for IFN-alpha, IFN-beta and IFN-omega that exploit the ability of these factors to inhibit proliferation of TF-1 cells induced by GM-CSF. The bioassays can be used also with Epo and TF-1 cells, or Epo and Epo-transfected UT-7 cells.

For further information on assays for cytokines see also: bioassays, cytokine assays.

The MxR assay (see: Mx) involves use of a genetically engineered Vero cell line to measure IFN-beta.


CLINICAL USE AND SIGNIFICANCE

IFN-beta can be used for topic treatment of condylomata acuminata. It is also suitable for the prophylactic use following surgical removal of large condylomas. Some studies suggest that IFN-beta tends to prevent disease activity in patients with multiple sclerosis.

IFN-beta in combination with IFN-alpha has been used in the treatment of chronic active hepatitis B and appears to be most promising if the disease has not lasted longer than 5 years. The antiviral activity of IFN-beta is demonstrated also in the treatment of severe childhood viral encephalitis.

A combination treatment in combination with acyclovir is more effective than treatment with acyclovir alone.

IFN-beta is a lipophilic molecule that should be particularly useful for local tumor therapy due to its specific pharmacokinetics. It is hardly removed from the tumor tissues after intralesional administration and hence also shows little systemic side effects. Head and neck squamous carcinomas, mammary and cervical carcinomas, and also malignant melanomas respond well to treatment with IFN-beta. IFN-beta also appears to be very promising for the adjuvant therapy of malignant melanomas with a high potential for metastasis. Response rates have been reported to be improved by combining IFN-beta with antineoplastic agents or other cytokines.

In many instances a combination of the various interferons (see: IFN) has been found to cause synergistic effects. The antiviral/antiproliferative/antitumor properties of IFN-beta is potentiated by febrile temperatures.



 

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