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Interferon gamma

Interferon gamma

Interferon gamma (IFN-?) is the sole member of the type II interferon family and is critical for both innate and adaptive immunity. IFN-? has a distinct structure and function as well as a more restricted expression pattern compared to its type I family members. The mature form of IFN-? is a glycosylated, noncovalent homodimer produced and secreted by activated lymphocytes. IFN-? binds to the IFN-?R1 receptor subunit which engages the IFN-?R2 receptor subunit to activate JAK1 and JAK2. The pleiotropic effects of IFN-? are mediated through the expression of hundreds of IFN-?-regulated genes including inflammatory signaling molecules, apoptotic regulators, and other transcription factors. The role of IFN-? in the activation of the immune response has led to its use in various clinical applications including fungal diseases as well as certain types of cancers and autoimmune diseases. Recombinant IFN-? has been approved by the FDA to reduce the severity of infections associated with Chronic Granulomatous Disease (CGD) and for the treatment of severe, malignant osteopetrosis. Additionally, IFN-? is crucial for tumor surveillance by the immune system and also has direct anti-tumor effects in some types of cancers. Elevated levels of IFN-? play an essential role in the development and severity of some autoimmune diseases which has led to the generation and testing of monoclonal antibodies to neutralize the effects of IFN-? in diseases such as Crohn?s diseases, rheumatoid arthritis, and systemic lupus erythematosus.

Swiss-Prot Accession Number: P01579


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Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. (2014) Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Nature. 2014 Nov 26;515(7528):563-7. doi: 10.1038/nature14011.

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Cigarette smoke induces molecular responses in respiratory tissues of ApoE-/- mice that are progressively deactivated upon cessation (2013) Bou? S, De Le?n H, Schlage WK, Peck MJ, Weiler H, Berges A, Vuillaume G, Martin F, Friedrichs B, Lebrun S, Meurrens K, Schracke N, Moehring M, Steffen Y, Schueller J, Vanscheeuwijck P, Peitsch MC, Hoeng J Toxicology, Available online 1 October 2013

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Preferential Replication of Systemically Delivered Oncolytic Vaccinia Virus in Focally Irradiated Glioma Xenografts (2012) Advani SJ, Buckel L, Chen NG, Scanderbeg DJ, Geissinger U, Zhang Q, Yu YA, Aguilar RJ, Mundt A, Szalay AA Clin Cancer Res. 2012 Feb 29. [Epub ahead of print]

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Preferential Colonization of Metastases by Oncolytic Vaccinia Virus Strain GLV-1h68 in a Human PC-3 Prostate Cancer Model in Nude Mice (2012) Donat U, Weibel S, Hess M, Stritzker J, H?rtl B, Sturm JB, Chen NG, Gentschev I, Szalay AA PLoS ONE 7(9): e45942

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Characterization of immunologically active drugs in a novel organotypic co-culture model of the human gut and whole blood (2012) Schmohl M, Schneiderhan-Marra N, Baur N, Hefner K, Blum M, Stein GM, Joos TO, Schmolz M Int Immunopharmacol. 2012 Dec;14(4):722-8

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A small animal peripheral challenge model of yellow fever using interferon-receptor deficient mice and the 17D-204 vaccine strain (2012) Thibodeaux BA, Garbinoa NC, Lissb NM, Piper J, Blair CD, Roehrig JT Vaccine

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Type I interferon and pattern recognition receptor signaling following particulate matter inhalation (2012) Erdely A, Antonini JM, Salmen-Muniz R, Liston A, Hulderman T, Simeonova PP, Kashon ML, Li S, Gu JK, Stone S, Chen BT, Frazer DG, Zeidler-Erdely PC Part Fibre Toxicol. 2012 Jul 9;9:25

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The Role of Residual Gadolinium in the Induction of Nephrogenic Systemic Fibrosis-Like Skin Lesions in Rats (2011) Pietsch H, Raschke M, Ellinger-Ziegelbauer H, Jost G, Walter J, Frenzel T, Lenhard D, H?tter J, Sieber MA Invest Radiol. 46: 48-56.

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Evidence for an antagonist form of the chemokine CXCL10 in patients chronically infected with HCV (2011) Casrouge A, Decalf J, Ahloulay M, Lababidi C, Mansour H, Vallet-Pichard A, Mallet V, Mottez E, Mapes J, Fontanet A, Pol S, Albert ML J Clin Invest. 121: 308-317.

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Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68 (2011) Gentschev I, M?ller M, Adelfinger M, Weibel S, Grummt F, Zimmermann M, Bitzer M, Heisig M, Zhang Q, Yu YA, Chen NG, Stritzker J, Lauer UM, Szalay AA PLoS ONE 6(7): e22069

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Discrimination of agonist and antagonist forms of CXCL10 in biologic samples (2011) Casrouge A, Bisiaux A, Stephen L, Schmolz M, Mapes J, Pfister C, Pol S, Mallet V, Albert ML Clin Exp Immunol. 2012 Jan;167(1):137-48

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Pathogenesis and Host Response in Syrian Hamsters following Intranasal Infection with Andes Virus (2011) Safronetz D, Zivcec M, LaCasse R, Feldmann F, Rosenke R, Long D, Haddock E, Brining D, Gardner D, Feldmann H, Ebihara H PLoS Pathog 7(12): e1002426

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G-protein-coupled receptor GPR21 knockout mice display improved glucose tolerance and increased insulin response (2011) Gardner J, Wu S, Ling L, Danao J, Li Y, Yeh WC, Tian H, Baribault H Biochemical and Biophysical Research Communications

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Attenuated Response of Aged Mice to Respiratory Francisella novicida Is Characterized by Reduced Cell Death and Absence of Subsequent Hypercytokinemia (2010) Mares CA, Sharma J, Ojeda SS, Li Q, Campos JA, Morris EG, Coalson JJ, Teale JM PLoS ONE 11: e14088.

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Significant growth inhibition of canine mammary carcinoma xenografts following treatment with oncolytic vaccinia virus GLV-1h68 (2010) Gentschev I, Ehrig K, Donat U, Hess M, Rudolph S, Chen N, Yu YA, Zhang Q, Bullerdiek J, Nolte I, Stritzker J, Szalay AA J Oncol. 2010:736907. Epub 2010 Jun 23

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Molecular Analyte Profiling of the Early Events and Tissue Conditioning Following Intravesical Bacillus Calmette-Guerin Therapy in Patients With Superficial Bladder Cancer. (2009) Bisiaux A, Thiounn N, Timsit MO, Eladaoui A, Chang HH, Mapes J, Mogenet A, Bresson JL, Pri? D, B?chet S, Baron C, Sadorge C, Thomas S, Albert EB, Albert PS, Albert ML J Urol 181: 1571-1580.

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Lethal Pulmonary Infection with Francisella Novicida is Associated with Severe Sepsis. (2009) Sharma J, Li Q, Mishra BB, Pena C, Teale JM J Leukoc Biol 86: 491-504.

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Regression of Human Pancreatic Tumor Xenografts in Mice After a Single Systemic Injection of Recombinant Vaccinia Virus GLV-1h68. (2009) Yu YA, Galanis C, Woo Y, Chen N, Zhang Q, Fong Y, Szalay AA Mol Cancer Ther 8: 141-151.

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Bacteria challenge in smoke-exposed mice exacerbates inflammation and skews the inflammatory profile (2009) Gaschler GJ, Skrtic M, Zavitz CC, Lindahl M, Onnervik PO, Murphy TF, Sethi S, St?mpfli MR. Am J Respir Crit Care Med. 179: 666-75.

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Ionizing radiation-induced gene modulations, cytokine content changes and telomere shortening in mouse fetuses exhibiting forelimb defects. (2008) Derradji H, Bekaert S, De Meyer T, Jacquet P, Abou-El-Ardat K, Ghardi M, Arlette M, Baatout S Dev Biol 322: 302-313.

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Serum biomarkers in a mouse model of bacterial-induced inflammatory bowel disease. (2008) Torrence AE, Brabb T, Viney JL, Bielefeldt-Ohmann H, Treuting P, Seamons A, Drivdahl R, Zeng W, Maggio-Price L Inflamm Bowel Dis 14: 480-490.

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Initial delay in the immune response to Francisella tularensis is followed by hypercytokinemia characteristic of severe sepsis and correlating with upregulation and release of damage-associated molecular patterns. (2008) Mares CA, Ojeda SS, Morris EG, Li Q, Teale JM Infect Immun 76: 3001-3010.

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Inhibition of experimental Sj?grens syndrome through immunization with HSP60 and its peptide amino acids 437-460 (2008) Delaleu N, Madureira AC, Immervoll H, Jonsson R Arthritis Rheum. Aug;58(8):2318-28

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Pulmonary delivery of adenovirus vector formulated with dexamethasone-spermine facilitates homologous vector re-administration. (2007) Price AR, Limberis MP, Wilson JM, Diamond SL Gene Ther 14: 1594-1604.

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TWEAK is a novel arthritogenic mediator. (2006) Perper SJ, Browning B, Burkly LC, Weng S, Gao C, Giza K, Su L, Tarilonte L, Crowell T, Rajman L, Runkel L, Scott M, Atkins GJ, Findlay DM, Zheng TS, Hess H J Immunol 177: 2610-2620.

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Effects of cidofovir treatment on cytokine induction in murine models of cowpox and vaccinia virus infection. (2006) Knorr CW, Allen SD, Torres AR, Smee DF Antiviral Res 72: 125-133.

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Multiplex proteomic approaches to sepsis research: case studies employing new technologies. (2005) Heuer JG, Cummins DJ, Edmonds BT Expert Rev Proteomics 2: 669-680.

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LXR-dependent gene expression is important for macrophage survival and the innate immune response. (2004) Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA, Pei L, Hogenesch J, Oconnell RM, Cheng G, Saez E, Miller JF, Tontonoz P Cell 119: 299-309.

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Validation of a new highly standardised, lab-independent whole-blood leukocyte function assay for clinical trials (ILCS). (2004) Schmolz M, Hurst TL, Bailey DM, Powell JR, Forsey RJ, Thompson JM, Williams C, Pawelec G Exp Gerontol 39: 667-671.

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