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Interleukin-6

Interleukin-6

Interleukin-6 (IL-6) is a secreted proinflammatory protein that is part of the IL-6 cytokine family. IL-6 is produced mainly by monocytes, macrophages, dendritic cells, and T cells, but other cells, such as epithelial cells, endothelial cells, fibroblasts, adipocytes, and keratinocytes, are capable of secreting IL-6 under inflammatory conditions. Several agents can induce IL-6 production, including pathogen-associated molecular patterns (PAMPs) such as toll-like receptor agonists and damage-associated molecular patterns (DAMPs) such as mitochondrial DNA. IL-6 signals through binding of either the membrane bound or soluble IL-6 receptor (mIL-6R, sIL-6) as it complexes and activates gp130. Membrane bound IL-6R expression is restricted to immune cells and hepatocytes. However, since nearly all cells express gp130, trans-signaling of IL-6 through binding to the sIL-6R can occur in any cell. IL-6 promotes induction of other inflammatory cytokines and chemokines and plays a role in recruitment of neutrophils and monocytes, promotion of B cell development, regulation of liver metabolism, and stimulation of tumor cell proliferation, survival and invasiveness. In addition, IL-6, in combination with TGF-a, induces development of TH17) cells and production of IL-17.

Swiss-Prot Accession Number: P05231


Bibliography

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A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimers Disease. (2015) Khan W, Aguilar C, Kiddle SJ, Doyle O, Thambisetty M, Muehlboeck S, Sattlecker M, Newhouse S, Lovestone S, Dobson R, Giampietro V, Westman E, Simmons A PLoS One

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Exploring effects of a natural combination medicine on exercise-induced inflammatory immune response: A double-blind RCT (2014) Pilat C, Frech T, Wagner A, Kr?ger K, Hillebrecht A, Pons-K?hnemann J, Scheibelhut C, B?deker RH, Mooren FC Scand J Med Sci Sports. 2014 Jun 12

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Genome-Wide Association Study of CSF Levels of 59 Alzheimers Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation (2014) Kauwe JS, Bailey MH, Ridge PG, Perry R, Wadsworth ME, Hoyt KL, Staley LA, Karch CM, Harari O, Cruchaga C, Ainscough BJ, Bales K, Pickering EH, Bertelsen S; Alzheimers Disease Neuroimaging Initiative, Fagan AM, Holtzman DM, Morris JC, Goate AM PLoS Genet

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IL-6 pathway-driven investigation of response to IL-6 receptor inhibition in rheumatoid arthritis (2013) Wang J, Platt A, Upmanyu R, Germer S, Lei G, Rabe C, Benayed R, Kenwright A, Hemmings A, Martin M, Harari O BMJ Open. 2013 Aug 19;3(8):e003199

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Suppression of Inflammation with Conditional Deletion of the Prostaglandin E2 EP2 Receptor in Macrophages and Brain Microglia (2013) Johansson JU, Pradhan S, Lokteva LA, Woodling NS, Ko N, Brown HD, Wang Q, Loh C, Cekanaviciute E, Buckwalter M, Manning-Bog AB, Andreasson KI J Neurosci. 2013 Oct 2;33(40):16016-16032

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Photoacoustic Imaging of Mesenchymal Stem Cells in Living Mice via Silica-Coated Gold Nanorods (2012) Jokerst JV, Thangaraj M, Kempen P, Sinclair R, Gambhir SS ACS Nano. 2012 Jun 10. [Epub ahead of print]

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STAT3 Is Activated by JAK2 Independent of Key Oncogenic Driver Mutations in Non-Small Cell Lung Carcinoma (2012) Looyenga BD, Hutchings D, Cherni I, Kingsley C, Weiss GJ, MacKeigan JP PLoS ONE 7(2): e30820

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In vivo and in vitro genetic evidence of involvement of neuregulin 1 in immune system dysregulation (2010) Marballi K, Quinones MP, Jimenez F, Escamilla MA, Ravent?s H, Soto-Bernardini MC, Ahuja SS, Walss-Bass C J Mol Med. 88: 1133-41.

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Validation of a Blood-Based Laboratory Test to Aid in the Confirmation of a Diagnosis of Schizophrenia (2010) Schwarz E, Izmailov R, Spain M, Barnes A, Mapes JP, Guest PC, Rahmoune H, Pietsch S, Leweke FM, Rothermundt M, Steiner J, Koethe D, Kranaster L, Ohrmann P, Suslow T, Levin Y, Bogerts B, (JM) van Beveren N, McAllister G, Weber N, Niebuhr D, Cowan D, Yolken RH, Bahn S Biomark Insights5: 39?47.

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Systemic levels of G-CSF and interleukin-6 determine the angiogenic potential of bone marrow resident monocytes. (2010) Gregory AD, Capoccia BJ, Woloszynek JR, Link DC J Leukoc Biol 88: 123-31.

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Distinct functions of activated protein C differentially attenuate acute kidney injury (2009) Gupta A, Gerlitz B, Richardson MA, Bull C, Berg DT, Syed S, Galbreath EJ, Swanson BA, Jones BE, Grinnell BW J Am Soc Nephrol. 20: 267-77.

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Characterization of the Inflammatory Response to a Highly Selective PDE4 Inhibitor in the Rat and the Identification of Biomarkers that Correlate with Toxicity. (2006) Dietsch GN, Dipalma CR, Eyre RJ, Pham TQ, Poole KM, Pefaur NB, Welch WD, Trueblood E, Kerns WD, Kanaly ST Toxicol Pathol 34: 39-51.

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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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