This product encodes Human Interferon gamma-1b (140 residues), produced from E. coli via conventional column chromatography. Production of this therapeutic protein is achieved by fermentation of a genetically engineered E.coli bacterium containing the DNA which encodes for the human protein. The sequence displayed is a cDNA sequence which codes for human interferon gamma, as described by Gray et. al. and not specifically interferon gamma 1b.
<0.001 EU per 1 μg of the peptide by the LAL method
Interferon gamma-1b is used for the treatment of Chronic granulomatous disease and Osteopetrosis.
Examples of Clinical Use:
Chronic granulomatous disease and Osteopetrosis
IFN gamma stimulates expression of the immunoglobulin heavy chain C gamma 3 and C gamma 2a germline transcripts in B cells. Many components of the antigen presentation pathways are also up-regulated by interferon gamma. It is also a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of type I interferons. The product may also help the body regulate the activity of fibroblasts. By directly blocking the multiplication of fibroblasts and inhibiting the production and action of TGF-b, a potent scar-inducing molecule, Interferon gamma-1b may prevent excessive scarring.
Mechanism of action:
Binds directly to the type II interferon gamma receptor IFNGR1, leading to a complex of IFNGR1 and IFNGR2. This activates JAK1 and JAK2 kinases which form a STAT1 docking site. This leads to STAT1 phosphorylation, nuclear translocation and initiation of gene transcription of multiple immune-related genes.
Interferon gamma-1b (IFNγ-1b) is a cytokine in the interferon class, an important class of proteins dedicated to carrying out intercellular communication to help regulate immune responses. Among its siblings, IFNα, β, and ω, it's been most widely celebrated for its pivotal role in the proper functioning of the immune system.
The discovery of IFNγ-1b dates back to the late 1970s-early 1980s, when its presence marked a breakthrough in comprehending how cells communicate to regulate immune responses. Over the years, its sophisticated structure and intriguing role in human diseases have remained in view.
The gene that encodes IFNγ-1b is found on human chromosome 12. Specifically, this occurs in the chromosomal region 12q15 within the locus tagged as IFNG. The gene comprises of four exons and three introns.
In terms of protein structure, IFNγ-1b can be described as a homodimeric protein, containing two identical chains attached. Each chain is unfolded and houses a series of Alpha helices categorized into helix A to F, with each helix separated by flexible loops counterbalanced by conserved residues.
Coming to the function of IFNγ-1b, it plays a dominant role in controlling and amplifying the immune response. Its primary function is to activate the macrophages that presents antigens to T cells. It also arbitrates immune response by stimulating the production of antibodies, encouraging antigen presentation, and promoting the expression of molecules vital for antigen presentation. Also, it differentiates helper T cells into Th1 cells which further stimulate cell-mediated immune response.
IFNγ-1b related signaling pathways
IFNγ-1b transfers information through several key signaling pathways, including the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. In this, IFNγ-1b binds to its receptor, inducing the phosphorylation and activation of JAK1 and JAK2. This leads to the recruitment and activation of STAT1, producing IFNγ-activated factor (GAF), which then drives gene expression. The MAPK/ERK pathway and the PI3K/Akt pathway are also triggered by IFNγ-1b, contributing to cell survival and anti-viral responses.
IFNγ-1b -related diseases
Associations of IFNγ-1b with various diseases have been reported. In chronic granulomatous disease (CGD), a rare inherited disorder that weakens the immune system, IFNγ-1b has shown to significantly reduce the frequency of serious infections. Additionally, decreased IFNγ-1b activity has often been found in autoimmune diseases, such as multiple sclerosis, highlighting its potential role in disease pathogenesis.
In terms of therapeutic application, IFNγ-1b has been employed as a drug treatment for several diseases. It's approved by the U.S. FDA for treating CGD and severe, malignant osteopetrosis. In the latter, IFNγ-1b stimulates the bone-resorbing activity of osteoclasts, thereby managing the progression of the disease. It's also under continual investigation for its efficacy against several other conditions, including cancers and several viral, bacterial, and fungal infections.
List of drug candidates related to IFNγ-1b
Several drug candidates related to Interferon gamma-1b are currently being investigated for their potential roles in treating a variety of conditions. These include Avonex (interferon beta-1a), an FDA-approved treatment for multiple sclerosis which works by modulating the body's immune system response. Another is Actimmune (interferon gamma-1b), which is employed as a therapeutic strategy for chronic granulomatous disease and malignant osteopetrosis. Further, combination therapies involving IFNγ-1b are also on the horizon, like in the case of severe acute respiratory syndrome (SARS), where it is combined with corticosteroids.
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