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==Induction of interferons== Production of interferons occurs mainly in response to microbes, such as viruses and bacteria, and their products. Binding of molecules uniquely found in microbes—viral [[glycoprotein]]s, viral [[RNA]], bacterial [[endotoxin]] (lipopolysaccharide), bacterial [[flagella]], [[CpG ODN|CpG motifs]]—by [[pattern recognition receptor]]s, such as membrane bound [[toll like receptor]]s or the cytoplasmic receptors [[DDX58|RIG-I]] or [[IFIH1|MDA5]], can trigger release of IFNs. Toll Like Receptor 3 ([[TLR 3|TLR3]]) is important for inducing interferons in response to the presence of [[double-stranded RNA viruses]]; the [[ligand]] for this receptor is [[DsRNA|double-stranded RNA (dsRNA)]]. After binding dsRNA, this receptor activates the transcription factors [[IRF3]] and [[NF-κB]], which are important for initiating synthesis of many inflammatory proteins. [[RNA interference]] technology tools such as siRNA or vector-based reagents can either silence or stimulate interferon pathways.<ref>{{cite journal | vauthors = Whitehead KA, Dahlman JE, Langer RS, Anderson DG | title = Silencing or stimulation? siRNA delivery and the immune system | journal = Annual Review of Chemical and Biomolecular Engineering | volume = 2 | pages = 77–96 | year = 2011 | pmid = 22432611 | doi = 10.1146/annurev-chembioeng-061010-114133 | s2cid = 28803811 }}</ref> Release of IFN from cells (specifically IFN-γ in lymphoid cells) is also induced by [[mitogen]]s. Other cytokines, such as [[interleukin 1]], [[interleukin 2]], [[interleukin-12]], [[Tumor necrosis factor-alpha|tumor necrosis factor]] and [[colony-stimulating factor]], can also enhance interferon production.<ref>{{cite journal | vauthors = Haller O, Kochs G, Weber F | title = Interferon, Mx, and viral countermeasures | journal = Cytokine & Growth Factor Reviews | volume = 18 | issue = 5–6 | pages = 425–433 | date = October–December 2007 | pmid = 17683972 | pmc = 7185553 | doi = 10.1016/j.cytogfr.2007.06.001 }}</ref>
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