[{"@context":"http:\/\/schema.org\/","@type":"BlogPosting","@id":"https:\/\/wiki.edu.vn\/en\/wiki40\/indoleamine-23-dioxygenase-wikipedia\/#BlogPosting","mainEntityOfPage":"https:\/\/wiki.edu.vn\/en\/wiki40\/indoleamine-23-dioxygenase-wikipedia\/","headline":"Indoleamine 2,3-dioxygenase – Wikipedia","name":"Indoleamine 2,3-dioxygenase – Wikipedia","description":"From Wikipedia, the free encyclopedia Mammalian protein found in Homo sapiens Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO EC 1.13.11.52) is a","datePublished":"2018-11-16","dateModified":"2018-11-16","author":{"@type":"Person","@id":"https:\/\/wiki.edu.vn\/en\/wiki40\/author\/lordneo\/#Person","name":"lordneo","url":"https:\/\/wiki.edu.vn\/en\/wiki40\/author\/lordneo\/","image":{"@type":"ImageObject","@id":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","height":96,"width":96}},"publisher":{"@type":"Organization","name":"Enzyklop\u00e4die","logo":{"@type":"ImageObject","@id":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","url":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","width":600,"height":60}},"image":{"@type":"ImageObject","@id":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/4\/4d\/PDB_2d0t_EBI.jpg\/180px-PDB_2d0t_EBI.jpg","url":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/4\/4d\/PDB_2d0t_EBI.jpg\/180px-PDB_2d0t_EBI.jpg","height":"135","width":"180"},"url":"https:\/\/wiki.edu.vn\/en\/wiki40\/indoleamine-23-dioxygenase-wikipedia\/","about":["Wiki"],"wordCount":8606,"articleBody":"From Wikipedia, the free encyclopediaMammalian protein found in Homo sapiensIndoleamine-pyrrole 2,3-dioxygenase (IDO or INDO EC 1.13.11.52) is a heme-containing enzyme physiologically expressed in a number of tissues and cells, such as the small intestine, lungs, female genital tract or placenta.[5] In humans is encoded by the IDO1 gene.[6] IDO is involved in tryptophan metabolism. It is one of three enzymes that catalyze the first and rate-limiting step in the kynurenine pathway, the O2-dependent oxidation of L-tryptophan to N-formylkynurenine, the others being indolamine-2,3-dioxygenase 2 (IDO2)[7] and tryptophan 2,3-dioxygenase (TDO).[8] IDO is an important part of the immune system and plays a part in natural defense against various pathogens.[9][10] It is produced by the cells in response to inflammation and has an immunosuppressive function because of its ability to limit T-cell function and engage mechanisms of immune tolerance.[11] Emerging evidence suggests that IDO becomes activated during tumor development, helping malignant cells escape eradication by the immune system. Expression of IDO has been described in a number of types of cancer, such as acute myeloid leukemia, ovarian cancer or colorectal cancer. IDO is part of the malignant transformation process and plays a key role in suppressing the anti-tumor immune response in the body, so inhibiting it could increase the effect of chemotherapy as well as other immunotherapeutic protocols.[12][13][14]Table of ContentsPhysiological function[edit]Clinical significance[edit]Inhibitors[edit]See also[edit]References[edit]External links[edit]Physiological function[edit]Indoleamine 2,3-dioxygenase is the first and rate-limiting enzyme of tryptophan catabolism through the kynurenine pathway.IDO is an important molecule in the mechanisms of tolerance and its physiological functions include the suppression of potentially dangerous inflammatory processes in the body.[15] IDO also plays a role in natural defense against microorganisms. Expression of IDO is induced by interferon-gamma, which explains why the expression increases during inflammatory diseases or even during tumorigenesis.[16] Since tryptophan is essential for the survival of pathogens, the activity of enzyme IDO destroys them. Microorganisms susceptible to tryptophan deficiency include bacteria of genus Streptococcus[17] or viruses such as herpes simplex[18] or measles.[19]One of the organs with high IDO expression is the placenta. In the 1990s, the immunosuppressive function of this enzyme was first described in mice due to the study of placental tryptophan metabolism. Thus, mammalian placenta, due to intensive tryptophan catabolism has the ability to suppress T cell activity, thereby contributing to its position of immunologically privileged tissue.[20]Clinical significance[edit]IDO is an immune checkpoint molecule in the sense that it is an immunomodulatory enzyme produced by alternatively activated macrophages and other immunoregulatory cells.[21] IDO is known to suppress T and NK cells, generate Tregs and myeloid-derived suppressor cells, and also supports angiogenesis.[12]These mechanisms are crucial in the process of carcinogenesis. IDO allows tumor cells to escape the immune system by two main mechanisms. The first mechanism is based on tryptophan depletion from the tumor microenvironment.[22] The second mechanism is based on the production of catabolic products called kynurenins, that are cytotoxic for T lymphocytes and NK cells.[23] Overexpression of human IDO (hIDO) is described in a variety of human tumor cell lineages and is often associated with poor prognosis.[24][25] Tumors with increased production of IDO include prostate, ovarian, lung or pancreatic cancer or acute myeloid leukemia.[26][27] Expression of IDO is under physiological conditions regulated by the Bin1 gene, which can be damaged by tumor transformation.[28]Emerging clinical studies suggest that combination of IDO inhibitors with classical chemotherapy and radiotherapy could restore immune control and provide a therapeutic response to generally resistant tumors. Enzyme IDO used by tumors to escape immune surveillance is currently in focus of research and drug discovery efforts,[29] as well as efforts to understand if it could be used as a biomarker for prognosis.[30]Inhibitors[edit]COX-2 inhibitors down-regulate indoleamine 2,3-dioxygenase, leading to a reduction in kynurenine levels as well as reducing proinflammatory cytokine activity.[citation needed]1-Methyltryptophan is a racemic compound that weakly inhibits indoleamine dioxygenase, but is also a very slow substrate. The specific racemer 1-methyl-D-tryptophan (known as indoximod) is in clinical trials for various cancers.Epacadostat (INCB24360) and navoximod (GDC-0919) are potent inhibitors of the indoleamine 2,3-dioxygenase enzyme and are in clinical trials for various cancers. BMS-986205 is also in clinical trials for cancer.See also[edit]References[edit]^ a b c GRCh38: Ensembl release 89: ENSG00000131203 – Ensembl, May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031551 – Ensembl, May 2017^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.^ Yamazaki F, Kuroiwa T, Takikawa O, Kido R (September 1985). “Human indolylamine 2,3-dioxygenase. Its tissue distribution, and characterization of the placental enzyme”. The Biochemical Journal. 230 (3): 635\u20138. doi:10.1042\/bj2300635. PMC\u00a01152665. PMID\u00a03877502.^ “Entrez Gene: INDO indoleamine-pyrrole 2,3 dioxygenase”.^ Prendergast GC, Metz R, Muller AJ, Merlo LM, Mandik-Nayak L (2014-11-20). “IDO2 in Immunomodulation and Autoimmune Disease”. Frontiers in Immunology. 5: 585. doi:10.3389\/fimmu.2014.00585. PMC\u00a04238401. PMID\u00a025477879.^ Badawy AA, Bano S (January 2016). “Tryptophan Metabolism in Rat Liver After Administration of Tryptophan, Kynurenine Metabolites, and Kynureninase Inhibitors”. International Journal of Tryptophan Research. 9: 51\u201365. doi:10.4137\/ijtr.s38190. PMC\u00a04982523. PMID\u00a027547037.^ Yoshida R, Hayaishi O (August 1978). “Induction of pulmonary indoleamine 2,3-dioxygenase by intraperitoneal injection of bacterial lipopolysaccharide”. Proceedings of the National Academy of Sciences of the United States of America. 75 (8): 3998\u20134000. Bibcode:1978PNAS…75.3998Y. doi:10.1073\/pnas.75.8.3998. PMC\u00a0392917. PMID\u00a0279015.^ Yoshida R, Urade Y, Tokuda M, Hayaishi O (August 1979). “Induction of indoleamine 2,3-dioxygenase in mouse lung during virus infection”. Proceedings of the National Academy of Sciences of the United States of America. 76 (8): 4084\u20136. Bibcode:1979PNAS…76.4084Y. doi:10.1073\/pnas.76.8.4084. PMC\u00a0383982. PMID\u00a0291064.^ Munn DH, Mellor AL (March 2013). “Indoleamine 2,3 dioxygenase and metabolic control of immune responses”. Trends in Immunology. 34 (3): 137\u201343. doi:10.1016\/j.it.2012.10.001. PMC\u00a03594632. PMID\u00a023103127.^ a b Prendergast GC, Smith C, Thomas S, Mandik-Nayak L, Laury-Kleintop L, Metz R, Muller AJ (July 2014). “Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer”. Cancer Immunology, Immunotherapy. 63 (7): 721\u201335. doi:10.1007\/s00262-014-1549-4. PMC\u00a04384696. PMID\u00a024711084.^ Munn DH, Mellor AL (March 2016). “IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance”. Trends in Immunology. 37 (3): 193\u2013207. doi:10.1016\/j.it.2016.01.002. PMC\u00a04916957. PMID\u00a026839260.^ Uyttenhove C, Pilotte L, Th\u00e9ate I, Stroobant V, Colau D, Parmentier N,  et\u00a0al. (October 2003). “Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase”. Nature Medicine. 9 (10): 1269\u201374. doi:10.1038\/nm934. PMID\u00a014502282. S2CID\u00a010618102.^ Romani L, Fallarino F, De Luca A, Montagnoli C, D’Angelo C, Zelante T,  et\u00a0al. (January 2008). “Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease”. Nature. 451 (7175): 211\u20135. Bibcode:2008Natur.451..211R. doi:10.1038\/nature06471. PMID\u00a018185592. S2CID\u00a04391121.^ Mellor AL, Lemos H, Huang L (2017-10-27). “Indoleamine 2,3-Dioxygenase and Tolerance: Where Are We Now?”. Frontiers in Immunology. 8: 1360. doi:10.3389\/fimmu.2017.01360. PMC\u00a05663846. PMID\u00a029163470.^ MacKenzie CR, Hadding U, D\u00e4ubener W (September 1998). “Interferon-gamma-induced activation of indoleamine 2,3-dioxygenase in cord blood monocyte-derived macrophages inhibits the growth of group B streptococci”. The Journal of Infectious Diseases. 178 (3): 875\u20138. doi:10.1086\/515347. PMID\u00a09728563.^ Adams O, Besken K, Oberd\u00f6rfer C, MacKenzie CR, Takikawa O, D\u00e4ubener W (March 2004). “Role of indoleamine-2,3-dioxygenase in alpha\/beta and gamma interferon-mediated antiviral effects against herpes simplex virus infections”. Journal of Virology. 78 (5): 2632\u20136. doi:10.1128\/jvi.78.5.2632-2636.2004. PMC\u00a0369218. PMID\u00a014963171.^ Obojes K, Andres O, Kim KS, D\u00e4ubener W, Schneider-Schaulies J (June 2005). “Indoleamine 2,3-dioxygenase mediates cell type-specific anti-measles virus activity of gamma interferon”. Journal of Virology. 79 (12): 7768\u201376. doi:10.1128\/jvi.79.12.7768-7776.2005. PMC\u00a01143631. PMID\u00a015919929.^ Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B,  et\u00a0al. (August 1998). “Prevention of allogeneic fetal rejection by tryptophan catabolism”. Science. 281 (5380): 1191\u20133. Bibcode:1998Sci…281.1191M. doi:10.1126\/science.281.5380.1191. PMID\u00a09712583.^ Moon YW, Hajjar J, Hwu P, Naing A (2015). “Targeting the indoleamine 2,3-dioxygenase pathway in cancer”. Journal for Immunotherapy of Cancer. 3: 51. doi:10.1186\/s40425-015-0094-9. PMC\u00a04678703. PMID\u00a026674411.^ Munn, David H.; Shafizadeh, Ebrahim; Attwood, John T.; Bondarev, Igor; Pashine, Achal; Mellor, Andrew L. (1999-05-03). “Inhibition of T Cell Proliferation by Macrophage Tryptophan Catabolism”. The Journal of Experimental Medicine. 189 (9): 1363\u20131372. doi:10.1084\/jem.189.9.1363. ISSN\u00a00022-1007. PMC\u00a02193062. PMID\u00a010224276.^ Frumento, Guido; Rotondo, Rita; Tonetti, Michela; Damonte, Gianluca; Benatti, Umberto; Ferrara, Giovanni Battista (2002-08-12). “Tryptophan-derived Catabolites Are Responsible for Inhibition of T and Natural Killer Cell Proliferation Induced by Indoleamine 2,3-Dioxygenase”. The Journal of Experimental Medicine. 196 (4): 459\u2013468. doi:10.1084\/jem.20020121. ISSN\u00a01540-9538. PMC\u00a02196046. PMID\u00a012186838.^ Okamoto, Aikou; Nikaido, Takashi; Ochiai, Kazunori; Takakura, Satoshi; Takao, Miho; Saito, Misato; Aoki, Yuko; Ishii, Nobuya; Yanaihara, Nozomu; Yamada, Kyosuke; Takikawa, Osamu (November 2007). “Ido serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells”. International Congress Series. 1304: 262\u2013273. doi:10.1016\/j.ics.2007.07.053. ISSN\u00a00531-5131.^ Inaba, Tomoko; Ino, Kazuhiko; Kajiyama, Hiroaki; Shibata, Kiyosumi; Yamamoto, Eiko; Kondo, Shinji; Umezu, Tomokazu; Nawa, Akihiro; Takikawa, Osamu; Kikkawa, Fumitaka (June 2010). “Indoleamine 2,3-dioxygenase expression predicts impaired survival of invasive cervical cancer patients treated with radical hysterectomy”. Gynecologic Oncology. 117 (3): 423\u2013428. doi:10.1016\/j.ygyno.2010.02.028. ISSN\u00a00090-8258. PMID\u00a020350764.^ Uyttenhove, Catherine; Pilotte, Luc; Th\u00e9ate, Ivan; Stroobant, Vincent; Colau, Didier; Parmentier, Nicolas; Boon, Thierry; Van den Eynde, Beno\u00eet J (2003-09-21). “Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase”. Nature Medicine. 9 (10): 1269\u20131274. doi:10.1038\/nm934. ISSN\u00a01078-8956. PMID\u00a014502282. S2CID\u00a010618102.^ Jiang, Tianze; Sun, Yingying; Yin, Zhichao; Feng, Sen; Sun, Liping; Li, Zhiyu (February 2015). “Research progress of indoleamine 2,3-dioxygenase inhibitors”. Future Medicinal Chemistry. 7 (2): 185\u2013201. doi:10.4155\/fmc.14.151. ISSN\u00a01756-8919. PMID\u00a025686005.^ Muller, Alexander J; DuHadaway, James B; Donover, P Scott; Sutanto-Ward, Erika; Prendergast, George C (2005-02-13). “Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy”. Nature Medicine. 11 (3): 312\u2013319. doi:10.1038\/nm1196. ISSN\u00a01078-8956. PMID\u00a015711557. S2CID\u00a012338548.^ Jiang T, Sun Y, Yin Z, Feng S, Sun L, Li Z (2015). “Research progress of indoleamine 2,3-dioxygenase inhibitors”. Future Medicinal Chemistry. 7 (2): 185\u2013201. doi:10.4155\/fmc.14.151. PMID\u00a025686005.^ Yu CP, Fu SF, Chen X, Ye J, Ye Y, Kong LD, Zhu Z (2018). “The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis”. Cellular Physiology and Biochemistry. 49 (1): 134\u2013143. doi:10.1159\/000492849. PMID\u00a030134237.External links[edit]PDB gallery2d0t: Crystal structure of 4-phenylimidazole bound form of human indoleamine 2,3-dioxygenase2d0u: Crystal structure of cyanide bound form of human indoleamine 2,3-dioxygenase"},{"@context":"http:\/\/schema.org\/","@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki40\/#breadcrumbitem","name":"Enzyklop\u00e4die"}},{"@type":"ListItem","position":2,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki40\/indoleamine-23-dioxygenase-wikipedia\/#breadcrumbitem","name":"Indoleamine 2,3-dioxygenase – Wikipedia"}}]}]