Interferon Gamma

Interferon-gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons.^[1] This interferon was originally called macrophage-activating factor.

Structure of IFN-γ

The IFN-γ monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region.^[2]^[3] This is shown in the structural models below. The α-helices in the core of the structure are numbered 1 to 6.

Line and cartoon representation of a IFN-γ monomer

The biologically active dimer is formed by anti-parallel inter-locking of the two monomers as shown below. In the cartoon model, one monomer is shown in red, the other in blue.

Line and cartoon representation of a IFN-γ dimer

The structural models shown above (see protein data bank code 1FG9) are all shortened at their C-termini by 17 amino acids. Full length IFN-γ is 143 amino acids in length, the models are 126 amino acids in length. Affinity for the glycosaminoglycan heparan sulphate resides solely within the deleted sequence of 17 amino acids.^[4]

Biological activity

In contrast to interferon-α and interferon-β which can be expressed by all cells, IFN-γ is secreted by T lymphocytes and NK cells only. Also known as immune interferon, IFN-γ is the only Type II interferon. It is serologically distinct from Type I interferons and it is acid-labile, while the type I variants are acid-stable.

IFN-γ has antiviral, immunoregulatory, and anti-tumour properties.^[5] It alters transcription in up to 30 genes producing a variety of physiological and cellular responses. Activation by IFN-γ is achieved by its interaction with a heterodimeric receptor consisting of IFNGR1 & IFNGR2 (interferon gamma receptors). IFN-γ binding to the receptor activates the JAK-STAT pathway. In addition, IFN-γ activates APCs and promotes Th1 differentiation by upregulating the transcription factor T-bet.

IFN-γ is the hallmark cytokine of Th1 cells (Th2 cells produce IL-4). NK cells and CD8+ cytotoxic T cells also produce IFN-γ. IFN-γ suppresses osteoclast formation by rapidly degrading the RANK adaptor protein TRAF6 in the RANK-RANKL signaling pathway, which otherwise stimulates the production of NFκB.

Therapeutic uses

Interferons are used to treat infectious diseases and cancer.

Scientists at the University of California at Berkeley have recently discovered that Diindolylmethane (DIM), a naturally occurring compound found in Brassica vegetables, upon oral consumption, is a direct and potent activator of Interferon-Gamma production and sensitivity within the body leading the way for the study of this compound as an anti-viral, anti-bacterial and anti-cancer therapeutic. As this is a dietary compound found in edible vegetables, this has caused a lot of excitement in the immunology field. This compound has also been shown to synergize with Interferon-Gamma in the expression and potentiation of the MHC-I Complex, leading to its study as a possible adjuvant to Interferon-gamma therapeutic models.

References

1. ^ Gray, P. W. and Goeddel, D. V. (1982). "Structure of the human immune interferon gene". Nature 298: 859-863.
2. ^ Ealick, S. E., Cook, W. J. et al. (1991). "Three-dimensional structure of recombinant human interferon-gamma". Science 252: 698-702.
3. ^ Thiel, D. J. et al. (2000). "Observation of an unexpected third receptor molecule in the crystal structure of human interferon-γ receptor complex". Structure 8 (9): 927-936.
4. ^ Vanhaverbeke, C. Simorre, J-P. et al. (2004). "NMR characterization of the interaction between the C-terminal domain of interferon-γ and heparin-derived oligosaccharides" 384: 93-99.
5. ^ Schroder et al. (2004). "Interferon-γ an overview of signals, mechanisms and functions". Journal of Leukocyte Biology 75: 163-189.

Hall, Steven S. (1997) A Commotion in the Blood. New York, New York: Henry Holt and Company. ISBN 0-8050-5841-9
Information on Interferon and how it relates to hepatitis c
Ikeda H, Old LJ, Schreiber RD (2002). "The roles of IFN gamma in protection against tumor development and cancer immunoediting.". Cytokine Growth Factor Rev. 13 (2): 95-109. PMID 11900986.
Chesler DA, Reiss CS (2003). "The role of IFN-gamma in immune responses to viral infections of the central nervous system.". Cytokine Growth Factor Rev. 13 (6): 441-54. PMID 12401479.
Dessein A, Kouriba B, Eboumbou C, et al. (2005). "Interleukin-13 in the skin and interferon-gamma in the liver are key players in immune protection in human schistosomiasis.". Immunol. Rev. 201: 180-90. DOI:10.1111/j.0105-2896.2004.00195.x. PMID 15361241.
Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection.". Curr. HIV Res. 3 (1): 87-94. PMID 15638726.
Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines.". Mini reviews in medicinal chemistry 5 (12): 1093-101. PMID 16375755.
Chiba H, Kojima T, Osanai M, Sawada N (2006). "The significance of interferon-gamma-triggered internalization of tight-junction proteins in inflammatory bowel disease.". Sci. STKE 2006 (316): pe1. DOI:10.1126/stke.3162006pe1. PMID 16391178.
Tellides G, Pober JS (2007). "Interferon-gamma axis in graft arteriosclerosis.". Circ. Res. 100 (5): 622-32. DOI:10.1161/01.RES.0000258861.72279.29. PMID 17363708.

• • [ e] Antivirals (primarily J05, also S01AD and D06BB)
Anti-herpesvirus	Aciclovir • Cidofovir • Docosanol • Famciclovir • Fomivirsen • Foscarnet • Ganciclovir • Idoxuridine • Penciclovir • Trifluridine • Tromantadine • Valaciclovir • Valganciclovir • Vidarabine
Anti-influenza agents	Arbidol • adamantane derivatives/M2 inhibitors (Amantadine, Rimantadine) • neuraminidase inhibitors (Oseltamivir, Peramivir, Zanamivir)
Antiretrovirals: NRTIs	Abacavir • Didanosine • Emtricitabine • Lamivudine • Stavudine • Zalcitabine • Zidovudine
Antiretrovirals: NtRTIs	Adefovir • Tenofovir
Antiretrovirals: NNRTIs	Efavirenz • Delavirdine • Nevirapine • Loviride
Antiretrovirals: PIs	Amprenavir • Atazanavir • Darunavir • Fosamprenavir • Indinavir • Lopinavir • Nelfinavir • Ritonavir • Saquinavir • Tipranavir
Antiretrovirals: Fusion inhibitors	Enfuvirtide
Other antiviral agents	general (Inosine, Interferon) • HIV (Maraviroc) • Picornavirus (Pleconaril) • Human papillomavirus/Molluscum contagiosum (Imiquimod, Podophyllotoxin) • Hepatitis C (Ribavirin, Viramidine)

• • [ e] Immunostimulants (L03)
Colony stimulating factors	Filgrastim - Molgramostim - Sargramostim - Lenograstim - Ancestim - Pegfilgrastim
Interferons	Interferon alpha natural - Interferon beta natural - Interferon gamma - Interferon alpha-2a - Interferon alpha-2b - Interferon alpha-n1 - Interferon beta-1a - Interferon beta-1b - Interferon alphacon-1 - Peginterferon alpha-2b - Peginterferon alpha-2a
Interleukins	Aldesleukin - Oprelvekin
Other cytokines and immunomodulators	Lentinan - Roquinimex - BCG vaccine - Pegademase - Pidotimod - - Poly ICLC - Thymopentin - Immunocyanin - Tasonermin - Melanoma vaccine - Glatiramer acetate - Histamine dihydrochloride

• • [ e] Cell signaling: cytokines
Autocrine motility factor - Chemokine - Hematopoietic (Stem cell factor, Colony-stimulating factor) - Hepatocyte growth factor - Interferon - Interleukin - Leukemia inhibitory factor - Lymphokine (Lymphotoxin, Transfer factor) - Monokine - Oncostatin M - Osteopontin - TGF beta - Tumor necrosis factor

• • [ e] Cytokines: interferons
Interferon type I	Interferon beta-1a - Interferon beta-1b - Pegylated interferon alfa-2a - Pegylated interferon alfa-2b
Interferon type II	Interferon-gamma
Interferon type III	Interleukin 28 - Interleukin 29

Hugo is a male given name, a latinized form of the name Hugh, a German/Teutonic name meaning "Bright in Mind and Spirit".

Hugo is one of the most popular names in Europe ranking as high as #2 in France, #6 in Spain, and #7 in Belgium in 2006.
..... Click the link for more information.

The Gene Ontology project, or GO, provides a controlled vocabulary to describe gene and gene product attributes in any organism. It can be broadly split into two parts.
..... Click the link for more information.

The Entrez Global Query Cross-Database Search System is a powerful federated search engine, or web portal that allows users to search many discrete health sciences databases at the National Center for Biotechnology Information (NCBI) website.
..... Click the link for more information.

Ensembl is a bioinformatics research project precisely a Genome Browser aiming to "develop a software system which produces and maintains automatic annotation on selected eukaryotic genomes".
..... Click the link for more information.

UniProt is the universal protein database, a central repository of protein data created by combining Swiss-Prot, TrEMBL and PIR. This makes it the world's most comprehensive resource on protein information.
..... Click the link for more information.

Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. These chemical signals are similar to hormones and neurotransmitters and are used to allow one cell to communicate with another.
..... Click the link for more information.

Interferons (IFNs) are natural proteins produced by the cells of the immune system of most vertebrates in response to challenges by foreign agents such as viruses, bacteria, parasites and tumor cells. Interferons belong to the large class of glycoproteins known as cytokines.
..... Click the link for more information.

Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. This data, typically obtained by X-ray crystallography or NMR spectroscopy, is submitted by biologists and biochemists from around the world, is released into the public domain,
..... Click the link for more information.

Glycosaminoglycans (GAGs) or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit.

Production

Protein cores made in the rough endoplasmic reticulum are posttranslationally modified by glycosyltransferases in the Golgi
..... Click the link for more information.

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins.
..... Click the link for more information.

T cells belong to a group of white blood cells known as lymphocytes and play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and NK cells by the presence of a special receptor on their cell surface that is called the
..... Click the link for more information.

Natural killer cells (or NK cells) are a type of cytotoxic lymphocyte which constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses.
..... Click the link for more information.

The JAK-STAT signaling pathway takes part in the regulation of cellular responses to cytokines and growth factors. Employing Janus kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs), the pathway transduces the signal carried by these extracellular
..... Click the link for more information.

antigen-presenting cell (APC) is a cell that displays foreign antigen complexed with MHC on its surface. T-cells may recognize this complex using their T-cell receptor (TCR).

Types

APCs fall into two categories: professional or non-professional.
..... Click the link for more information.

T helper cells (also known as effector T cells or T_h cells) are a sub-group of lymphocytes (a type of white blood cell or leukocyte) that plays an important role in establishing and maximizing the capabilities of the immune system.
..... Click the link for more information.

This article or section may be confusing or unclear for some readers.
Please [improve the article] or discuss this issue on the talk page. This article has been tagged since December 2006.
..... Click the link for more information.

IL4, Il-4, or IL-4 may refer to:

Ilyushin Il-4, a Soviet World War II bomber
Interleukin-4, a cytokine that stimulates the proliferation of activated B-cells

..... Click the link for more information.

cytotoxic T cell (also known as T_C, CTL, T-Killer cell or killer T cell) belongs to a sub-group of T lymphocytes (a type of white blood cell) which are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with
..... Click the link for more information.

An osteoclast (from the Greek words for "bone" and "broken") is a type of bone cell that removes bone tissue by removing the bone's mineralized matrix. This process is known as bone resorption.
..... Click the link for more information.

RANK (Receptor Activator of Nuclear Factor κ B), also known as TRANCE Receptor, is a type I membrane protein which is expressed on the surface of osteoclasts and is involved in the activation of osteoclasts upon ligand binding.
..... Click the link for more information.

TRAF6 is a TRAF protein.

External links

MeSH TRAF6

..... Click the link for more information.

RANKL (Receptor Activator for Nuclear Factor κ B Ligand), also known as TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and ODF (osteoclast differentiation factor) is a molecule important in bone metabolism.
..... Click the link for more information.

Brassica

Species

See text.

Brassica (BrÃ¡s-si-ca) is a genus of plants in the mustard family (Brassicaceae). The members of the genus may be collectively known either as cabbages, or as mustards.
..... Click the link for more information.

This article is copied from an article on Wikipedia.org - the free encyclopedia created and edited by online user community. The text was not checked or edited by anyone on our staff. Although the vast majority of the wikipedia encyclopedia articles provide accurate and timely information please do not assume the accuracy of any particular article. This article is distributed under the terms of GNU Free Documentation License.

Herod_Archelaus

iPedia Free Information Center