WordNet

a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
any of various protein molecules secreted by cells of the immune system that serve to regulate the immune system

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=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/06/19 16:21:35」(JST)

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Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. In humans, it is encoded by the IL6 gene.^[1]

IL-6 is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other tissue damage leading to inflammation. IL-6 also plays a role in fighting infection, as IL-6 has been shown in mice to be required for resistance against bacterium Streptococcus pneumoniae.^[2]

IL-6 is also considered a myokine, a cytokine produced from muscle, and is elevated in response to muscle contraction.^[3] It is significantly elevated with exercise, and precedes the appearance of other cytokines in the circulation. During exercise, it is thought to act in a hormone-like manner to mobilize extracellular substrates and/or augment substrate delivery.^[4]

Additionally, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. IL-6's role as an anti-inflammatory cytokine is mediated through its inhibitory effects on TNF-alpha and IL-1, and activation of IL-1ra and IL-10.

Function[edit]

IL-6 is one of the most important mediators of fever and of the acute phase response. It is capable of crossing the blood brain barrier^[5] and initiating synthesis of PGE₂ in the hypothalamus, thereby changing the body's temperature setpoint. In muscle and fatty tissue, IL-6 stimulates energy mobilization which leads to increased body temperature. IL-6 can be secreted by macrophages in response to specific microbial molecules, referred to as pathogen associated molecular patterns (PAMPs). These PAMPs bind to highly important group of detection molecules of the innate immune system, called pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). These are present on the cell surface and intracellular compartments and induce intracellular signaling cascades that give rise to inflammatory cytokine production.

IL-6 is also essential for hybridoma growth and is found in many supplemental cloning media such as briclone. Inhibitors of IL-6 (including estrogen) are used to treat postmenopausal osteoporosis. IL-6 is also produced by adipocytes and is thought to be a reason why obese individuals have higher endogeneous levels of CRP.^[6] Intranasally administered IL-6 has been shown to improve sleep-associated consolidation of emotional memories.^[7]

IL-6 is responsible for stimulating acute phase protein synthesis, as well as the production of neutrophils in the bone marrow. It supports the growth of B cells and is antagonistic to regulatory T cells.

Receptor[edit]

Main article: Interleukin-6 receptor

IL-6 signals through a cell-surface type I cytokine receptor complex consisting of the ligand-binding IL-6Rα chain (CD126), and the signal-transducing component gp130 (also called CD130). CD130 is the common signal transducer for several cytokines including leukemia inhibitory factor (LIF), ciliary neurotropic factor, oncostatin M, IL-11 and cardiotrophin-1, and is almost ubiquitously expressed in most tissues. In contrast, the expression of CD126 is restricted to certain tissues. As IL-6 interacts with its receptor, it triggers the gp130 and IL-6R proteins to form a complex, thus activating the receptor. These complexes bring together the intracellular regions of gp130 to initiate a signal transduction cascade through certain transcription factors, Janus kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs).^[8]

IL-6 is probably the best studied of the cytokines that use gp130, also known as IL-6 signal transducer (IL6ST), in their signalling complexes. Other cytokines that signal through receptors containing gp130 are Interleukin 11 (IL-11), Interleukin 27 (IL-27), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), leukemia inhibitory factor (LIF), oncostatin M (OSM), Kaposi's sarcoma-associated herpesvirus interleukin 6 like protein (KSHV-IL6).^[9] These cytokines are commonly referred to as the IL-6 like or gp130 utilising cytokines ^[10]

In addition to the membrane-bound receptor, a soluble form of IL-6R (sIL-6R) has been purified from human serum and urine. Many neuronal cells are unresponsive to stimulation by IL-6 alone, but differentiation and survival of neuronal cells can be mediated through the action of sIL-6R. The sIL-6R/IL-6 complex can stimulate neurites outgrowth promote survival of neurons, hence may be important in nerve regeneration through remyelination.

Interactions[edit]

Interleukin 6 has been shown to interact with interleukin-6 receptor.^[11]^[12]^[13] and glycoprotein 130.^[14]

Role in disease[edit]

IL-6 is relevant to many diseases such as diabetes,^[15] atherosclerosis,^[16] depression,^[17] Alzheimer's Disease,^[18] systemic lupus erythematosus,^[19] multiple myeloma,^[20] prostate cancer,^[21] Behçet's disease,^[22] and rheumatoid arthritis.^[23]

Advanced/metastatic cancer patients have higher levels of IL-6 in their blood.^[24] Hence there is an interest in developing anti-IL-6 agents as therapy against many of these diseases.^[25]^[26] The first such is tocilizumab which has been approved for rheumatoid arthritis. Another, ALD518, is in clinical trials.

Epigenetic modifications and disease[edit]

IL-6 has been shown to lead to several neurological diseases through its impact on epigenetic modification within the brain.^[27]^[28]^[29]^[30] IL-6 activates the Phosphoinositide 3-kinase (PI3K) pathway, and a downstream target of this pathway is the protein kinase B (PKB) (Hodge et al., 2007). IL-6 activated PKB can phosphorylate the nuclear localization signal on DNA methyltransferase-1(DNMT1).^[31] This phosphorylation causes movement of DNMT1 to the nucleus, where it can be transcribed.^[31] DNMT1 recruits other DNMTs, including DNMT3A and DNMT3B, which, as a complex, recruit HDAC1.^[30] This complex adds methyl groups to CpG islands on gene promoters, repressing the chromatin structure surrounding the DNA sequence and inhibiting transcriptional machinery from accessing the gene to induce transcription.^[30] Increased IL-6, therefore, can hypermethylate DNA sequences and subsequently decrease gene expression through its effects on DNMT1 expression.^[29]

Schizophrenia[edit]

The induction of epigenetic modification by IL-6 has been proposed as a mechanism in the pathology of schizophrenia through the hypermethylation and repression of the GAD67 promoter.^[30] This hypermethylation may potentially lead to the decreased GAD67 levels seen in schizophrenic brains.^[32] GAD67 may be involved in the pathology of schizophrenia through its effect on GABA levels and on neural oscillations.^[33] Neural oscillations occur when inhibitory GABAergic neurons fire synchronously and cause inhibition of a multitude of target excitatory neurons at the same time, leading to a cycle of inhibition and disinhibition.^[33] These neural oscillations are impaired in schizophrenics, and these alterations may be responsible for both positive and negative symptoms of schizophrenia.^[34]

Depression[edit]

The epigenetic effects IL-6 have also been implicated in the pathology of depression. The effects of IL-6 on depression are mediated through the repression of brain-derived neurotrophic factor (BDNF) expression in the brain; DNMT1 hypermethylates the BDNF promoter and reduces BDNF levels.^[35] Altered BDNF function has been implicated in depression,^[36] which is likely due to epigenetic modification following IL-6 upregulation.^[35] BDNF is a neutrophic factor that is implicated in spine formation, density and morphology on neurons.^[37] Downregulation of BDNF, therefore, may cause decreased connectivity in the brain. Depression is marked by altered connectivity, particularly between the anterior cingulate cortex and several other limbic areas, such as the hippocampus.^[38] The anterior cingulate cortex is responsible for detecting incongruences between expectation and perceived experience.^[39] Altered connectivity of the anterior cingulate cortex in depression, therefore, may cause altered emotions following certain experiences, leading to depressive reactions.^[39] This altered connectivity is mediated by IL-6 and its effect on epigenetic regulation of BDNF.^[35]

References[edit]

^ Ferguson-Smith AC, Chen YF, Newman MS, May LT, Sehgal PB, Ruddle FH (April 1988). "Regional localization of the interferon-beta 2/B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7p15-p21". Genomics 2 (3): 203–208. doi:10.1016/0888-7543(88)90003-1. PMID 3294161.
^ van der Poll T, Keogh CV, Guirao X, Buurman WA, Kopf M, Lowry SF (1997). "Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia". J Infect Dis 176 (2): 439–444. doi:10.1086/514062. PMID 9237710.
^ Febbraio MA, Pedersen BK (2005). "Contraction-induced myokine production and release: is skeletal muscle an endocrine organ?". Exerc Sport Sci Rev 33 (3): 114–119. doi:10.1097/00003677-200507000-00003. PMID 16006818.
^ Petersen AM, Pedersen BK (April 2005). "The anti-inflammatory effect of exercise". J. Appl. Physiol. 98 (4): 1154–1162. doi:10.1152/japplphysiol.00164.2004. PMID 15772055.
^ Banks WA, Kastin AJ, Gutierrez EG (September 1994). "Penetration of interleukin-6 across the murine blood–brain barrier". Neurosci. Lett. 179 (1–2): 53–6. doi:10.1016/0304-3940(94)90933-4. PMID 7845624.
^ Bastard J, Jardel C, Delattre J, Hainque B et al. (1999). "Evidence for a Link Between Adipose Tissue Interleukin-6 Content and Serum C-Reactive Protein Concentrations in Obese Subjects". Circulation 99 (16): 2219–2222. doi:10.1161/01.CIR.99.16.2219.c.
^ Benedict C, Scheller J, Rose-John S, Born J, Marshall L (October 2009). "Enhancing influence of intranasal interleukin-6 on slow-wave activity and memory consolidation during sleep". FASEB J. 23 (10): 3629–3636. doi:10.1096/fj.08-122853. PMID 19546306.
^ Heinrich PC, Behrmann, I, Müller-Newen G, Schaper F, Graeve L (1998). "Interleukin-6 type cytokine signalling through the gp130(Jak/STAT pathway". Biochem. J. 334 (Pt 2): 297–314. PMC 1219691. PMID 9716487.
^ Kishimoto T, Akira S, Narazaki M, Taga T (1995). "Interleukin-6 family of cytokines and gp130". Blood 86 (4): 1243–54. PMID 7632928.
^ Heinrich PC, Behrmann I, Haan, S, Hermanns, HM, Müller-Newen G, Schaper, F (2003). "Principles of interleukin-6-type cytokine signalling and its regulation". Biochem. J. 374 (Pt 1): 1–20. doi:10.1042/BJ20030407. PMC 1223585. PMID 12773095.
^ Schwantner A, Dingley AJ, Ozbek S, Rose-John S, Grötzinger J (January 2004). "Direct determination of the interleukin-6 binding epitope of the interleukin-6 receptor by NMR spectroscopy". J. Biol. Chem. 279 (1): 571–576. doi:10.1074/jbc.M311019200. PMID 14557255.
^ Schuster B, Kovaleva M, Sun Y, Regenhard P, Matthews V, Grötzinger J, Rose-John S, Kallen KJ (March 2003). "Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF". J. Biol. Chem. 278 (11): 9528–9535. doi:10.1074/jbc.M210044200. PMID 12643274.
^ Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T (August 1989). "Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130". Cell 58 (3): 573–581. doi:10.1016/0092-8674(89)90438-8. PMID 2788034.
^ Kallen KJ, zum Büschenfelde KH, Rose-John S (March 1997). "The therapeutic potential of interleukin-6 hyperagonists and antagonists". Expert Opin Investig Drugs 6 (3): 237–266. doi:10.1517/13543784.6.3.237. PMID 15989626.
^ Kristiansen OP, Mandrup-Poulsen T (December 2005). "Interleukin-6 and diabetes: the good, the bad, or the indifferent?". Diabetes. 54 Suppl 2: S114–24. doi:10.2337/diabetes.54.suppl_2.S114. PMID 16306329.
^ Dubiński A, Zdrojewicz Z (April 2007). "[The role of interleukin-6 in development and progression of atherosclerosis]". Pol. Merkur. Lekarski (in Polish) 22 (130): 291–4. PMID 17684929.
^ Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL (March 2010). "A meta-analysis of cytokines in major depression". Biological Psychiatry 67 (5): 446–457. doi:10.1016/j.biopsych.2009.09.033. PMID 20015486.
^ Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N (November 2010). "A meta-analysis of cytokines in Alzheimer's disease". Biological Psychiatry 68 (10): 930–941. doi:10.1016/j.biopsych.2010.06.012. PMID 20692646.
^ Tackey E, Lipsky PE, Illei GG (2004). "Rationale for interleukin-6 blockade in systemic lupus erythematosus". Lupus 13 (5): 339–343. doi:10.1191/0961203304lu1023oa. PMC 2014821. PMID 15230289.
^ Gadó K, Domján G, Hegyesi H, Falus A (2000). "Role of INTERLEUKIN-6 in the pathogenesis of multiple myeloma". Cell Biol. Int. 24 (4): 195–209. doi:10.1006/cbir.2000.0497. PMID 10816321.
^ Smith PC, Hobisch A, Lin DL, Culig Z, Keller ET (March 2001). "Interleukin-6 and prostate cancer progression". Cytokine Growth Factor Rev. 12 (1): 33–40. doi:10.1016/S1359-6101(00)00021-6. PMID 11312117.
^ Hirohata S, Kikuchi H (dec 2012). "Changes in biomarkers focused on differences in disease course or treatment in patients with neuro-Behçet's disease.". Internal Medicine 51 (24): 3359–65. doi:10.2169/internalmedicine.51.85834. PMID 23257520.
^ Nishimoto N (May 2006). "Interleukin-6 in rheumatoid arthritis". Curr Opin Rheumatol 18 (3): 277–281. doi:10.1097/01.bor.0000218949.19860.d1. PMID 16582692.
^ "Cancer Patients Typically Have Increased Interleukin-6 Levels". American Society of Clinical Oncology 2006 Annual Meeting, Abstracts 8632 and 8633. Medscape.com. 2006-06-26.
^ Barton BE (August 2005). "Interleukin-6 and new strategies for the treatment of cancer, hyperproliferative diseases and paraneoplastic syndromes". Expert Opin. Ther. Targets 9 (4): 737–752. doi:10.1517/14728222.9.4.737. PMID 16083340.
^ Smolen JS, Maini RN (2006). "Interleukin-6: a new therapeutic target". Arthritis Res. Ther. 8 Suppl 2 (Suppl 2): S5. doi:10.1186/ar1969. PMC 3226077. PMID 16899109.
^ Smith SE, Li J, Garbett K, Mirnics K, Patterson PH (October 2007). "Maternal immune activation alters fetal brain development through interleukin-6". J. Neurosci. 27 (40): 10695–702. doi:10.1523/JNEUROSCI.2178-07.2007. PMC 2387067. PMID 17913903.
^ Kaiser L, Fritz RS, Straus SE, Gubareva L, Hayden FG (July 2001). "Symptom pathogenesis during acute influenza: interleukin-6 and other cytokine responses". J. Med. Virol. 64 (3): 262–8. doi:10.1002/jmv.1045. PMID 11424113.
^ ^a ^b Foran E, Garrity-Park MM, Mureau C, Newell J, Smyrk TC, Limburg PJ, Egan LJ (April 2010). "Upregulation of DNA methyltransferase-mediated gene silencing, anchorage-independent growth, and migration of colon cancer cells by interleukin-6". Mol. Cancer Res. 8 (4): 471–81. doi:10.1158/1541-7786.MCR-09-0496. PMID 20354000.
^ ^a ^b ^c ^d Kundakovic M, Chen Y, Guidotti A, Grayson DR (February 2009). "The reelin and GAD67 promoters are activated by epigenetic drugs that facilitate the disruption of local repressor complexes". Mol. Pharmacol. 75 (2): 342–54. doi:10.1124/mol.108.051763. PMC 2684898. PMID 19029285.
^ ^a ^b Hodge DR, Cho E, Copeland TD, Guszczynski T, Yang E, Seth AK, Farrar WL (2007). "IL-6 enhances the nuclear translocation of DNA cytosine-5-methyltransferase 1 (DNMT1) via phosphorylation of the nuclear localization sequence by the AKT kinase". Cancer Genomics Proteomics 4 (6): 387–98. PMID 18204201.
^ Guidotti A, Auta J, Davis JM, Di-Giorgi-Gerevini V, Dwivedi Y, Grayson DR, Impagnatiello F, Pandey G, Pesold C, Sharma R, Uzunov D, Costa E, DiGiorgi Gerevini V (November 2000). "Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study". Arch. Gen. Psychiatry 57 (11): 1061–9. doi:10.1001/archpsyc.57.11.1061. PMID 11074872.
^ ^a ^b Gandal MJ, Sisti J, Klook K, Ortinski PI, Leitman V, Liang Y, Thieu T, Anderson R, Pierce RC, Jonak G, Gur RE, Carlson G, Siegel SJ (2012). "GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction". Transl Psychiatry 2: e142. doi:10.1038/tp.2012.69. PMC 3410621. PMID 22806213.
^ Uhlhaas PJ, Singer W (February 2010). "Abnormal neural oscillations and synchrony in schizophrenia". Nat. Rev. Neurosci. 11 (2): 100–13. doi:10.1038/nrn2774. PMID 20087360.
^ ^a ^b ^c Sharma RP, Tun N, Grayson DR (2008). "Depolarization induces downregulation of DNMT1 and DNMT3a in primary cortical cultures". Epigenetics 3 (2): 74–80. doi:10.4161/epi.3.2.6103. PMID 18536530.
^ Hwang JP, Tsai SJ, Hong CJ, Yang CH, Lirng JF, Yang YM (December 2006). "The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression". Neurobiol. Aging 27 (12): 1834–7. doi:10.1016/j.neurobiolaging.2005.10.013. PMID 16343697.
^ Ethell IM, Pasquale EB (February 2005). "Molecular mechanisms of dendritic spine development and remodeling". Prog. Neurobiol. 75 (3): 161–205. doi:10.1016/j.pneurobio.2005.02.003. PMID 15882774.
^ Greicius MD, Flores BH, Menon V, Glover GH, Solvason HB, Kenna H, Reiss AL, Schatzberg AF (September 2007). "Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus". Biol. Psychiatry 62 (5): 429–37. doi:10.1016/j.biopsych.2006.09.020. PMC 2001244. PMID 17210143.
^ ^a ^b Somerville LH, Heatherton TF, Kelley WM (August 2006). "Anterior cingulate cortex responds differentially to expectancy violation and social rejection". Nat. Neurosci. 9 (8): 1007–8. doi:10.1038/nn1728. PMID 16819523.

External links[edit]

IL-6 expression in various cancers

UpToDate Contents

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1. リウマチ性疾患におけるサイトカインネットワーク：治療の意味 cytokine networks in rheumatic diseases implications for therapy
2. リウマチ性疾患における生物学的製剤の概要 overview of biologic agents in the rheumatic diseases
3. 血管新生阻害剤の概要 overview of angiogenesis inhibitors
4. リウマチ性疾患におけるサイトカインの役割 role of cytokines in rheumatic diseases
5. 心不全における一酸化窒素、その他のホルモン、サイトカイン、およびケモカイン nitric oxide other hormones cytokines and chemokines in heart failure

English Journal

Absence of Suppressor of Cytokine Signaling-2 turns cardiomyocytes unresponsive to LIF-dependent increase in Ca2+ levels.

Rocha-Resende C1, Jesus IC1, Roman-Campos D2, Miranda AS1, Alves F1, Resende RR3, Cruz JD4, Machado FS1, Guatimosim S5.
American journal of physiology. Cell physiology.Am J Physiol Cell Physiol.2017 Jan 25:ajpcell.00004.2016. doi: 10.1152/ajpcell.00004.2016. [Epub ahead of print]
Little is known regarding the role of the Suppressor of Cytokine Signaling (SOCS) in the control of cytokine signaling in cardiomyocytes. We investigated the consequences of SOCS2 ablation for Leukemia Inhibitory Factor (LIF)-induced enhancement of intracellular Ca2+ ([Ca2+]i) transient by performin
PMID 28122728

Opposing Roles of Acetylation and Phosphorylation in LIFR-Dependent Self-Renewal Growth Signaling in Mouse Embryonic Stem Cells.

Wang XJ1, Qiao Y2, Xiao MM3, Wang L4, Chen J5, Lv W4, Xu L6, Li Y6, Wang Y3, Tan MD3, Huang C3, Li J4, Zhao TC7, Hou Z8, Jing N9, Chin YE10.
Cell reports.Cell Rep.2017 Jan 24;18(4):933-946. doi: 10.1016/j.celrep.2016.12.081.
LIF promotes self-renewal of mouse embryonic stem cells (mESCs), and in its absence, the cells differentiate. LIF binds to the LIF receptor (LIFR) and activates the JAK-STAT3 pathway, but it remains unknown how the receptor complex triggers differentiation or self-renewal. Here, we report that the L
PMID 28122243

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry.

Larsen JV1, Petersen CM2.
Journal of visualized experiments : JoVE.J Vis Exp.2017 Jan 6;(119). doi: 10.3791/55019.
The heterodimeric cytokine Cardiotrophin-like Cytokine:Cytokine-like Factor-1 (CLC:CLF-1) targets the glycosylphosphatidylinositol (GPI)-anchored CNTFRα to form a trimeric complex that subsequently recruits glycoprotein 130/Leukemia Inhibitory Factor Receptor-β (gp130/LIFRβ) for signaling. Both C
PMID 28117780

Japanese Journal

Characterization of two putative cytokine receptors, gp130 and ciliary neurotrophic factor receptor, from terrestrial salamanders

Kiemnec-Tyburczy Karen M.,Watts Richard A.,Arnold Stevan J.
Genes & Genetic Systems 86(2), 131-137, 2011
… Cytokines of the gp130 family are fundamental regulators of immune responses and signal through multimeric receptors to initiate intracellular second-messenger cascades. … Here, we provide the first characterization of two full-length gp130 cytokine receptors from the cDNA of the red-legged salamander (Plethodon shermani). … The first, gp130 (2745 bp), is a common signaling receptor for several multi-functional cytokines in vertebrates. …
NAID 130000758291

Mimicry of Erythropoietin and Interleukin-6 Signalling by an Antibody/Cytokine Receptor Chimera in Murine Myeloid 32D Cells

KAWAHARA Masahiro,UEDA Hiroshi,TSUMOTO Kouhei,KUMAGAI Izumi,NAGAMUNE Teruyuki
The journal of biochemistry 141(4), 563-571, 2007-04-01
NAID 10020100276

「サイトカイン受容体gp130」

Interleukin 6 (interferon, beta 2)
	; PDB rendering based on 1ALU.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1ALU, 1IL6, 1P9M, 2IL6
Identifiers
Symbols	IL6; BSF2; HGF; HSF; IFNB2; IL-6
External IDs	OMIM: 147620 MGI: 96559 HomoloGene: 502 ChEMBL: 1795129 GeneCards: IL6 Gene
Gene Ontology
Molecular function	• cytokine activity; • interleukin-6 receptor binding; • growth factor activity;
Cellular component	• extracellular region; • extracellular space; • interleukin-6 receptor complex; • external side of plasma membrane;
Biological process	• neutrophil apoptotic process; • hepatic immune response; • neutrophil mediated immunity; • monocyte chemotaxis; • positive regulation of acute inflammatory response; • positive regulation of leukocyte chemotaxis; • negative regulation of protein kinase activity; • acute-phase response; • inflammatory response; • humoral immune response; • aging; • positive regulation of cell proliferation; • negative regulation of cell proliferation; • regulation of cell shape; • response to heat; • response to cold; • response to mechanical stimulus; • regulation of vascular endothelial growth factor production; • negative regulation of lipid storage; • cell growth; • cytokine-mediated signaling pathway; • platelet activation; • response to caffeine; • endocrine pancreas development; • neuron projection development; • response to nutrient levels; • response to peptidoglycan; • response to lipopolysaccharide; • positive regulation of chemokine production; • positive regulation of interleukin-6 production; • response to insulin stimulus; • negative regulation of collagen biosynthetic process; • positive regulation of peptidyl-serine phosphorylation; • positive regulation of protein import into nucleus, translocation; • positive regulation of T cell proliferation; • T cell activation; • response to drug; • positive regulation of tyrosine phosphorylation of Stat3 protein; • defense response to protozoan; • regulation of apoptotic process; • negative regulation of apoptotic process; • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; • response to amino acid stimulus; • positive regulation of MAPK cascade; • negative regulation of chemokine biosynthetic process; • regulation of circadian sleep/wake cycle, non-REM sleep; • positive regulation of nitric oxide biosynthetic process; • cell redox homeostasis; • negative regulation of fat cell differentiation; • positive regulation of T-helper 2 cell differentiation; • positive regulation of neuron differentiation; • positive regulation of osteoblast differentiation; • negative regulation of gluconeogenesis; • positive regulation of translation; • positive regulation of DNA replication; • regulation of angiogenesis; • positive regulation of transcription, DNA-dependent; • positive regulation of transcription from RNA polymerase II promoter; • positive regulation of JAK-STAT cascade; • response to antibiotic; • muscle cell homeostasis; • bone remodeling; • negative regulation of hormone secretion; • negative regulation of muscle organ development; • positive regulation of smooth muscle cell proliferation; • positive regulation of epithelial cell proliferation; • negative regulation of cytokine secretion; • positive regulation of peptidyl-tyrosine phosphorylation; • defense response to Gram-negative bacterium; • defense response to Gram-positive bacterium; • positive regulation of B cell activation; • positive regulation of immunoglobulin secretion; • positive regulation of sequence-specific DNA binding transcription factor activity; • positive regulation of NF-kappaB transcription factor activity; • response to glucocorticoid stimulus; • response to calcium ion; • response to electrical stimulus; • defense response to virus; • positive regulation of protein kinase B signaling cascade; • positive regulation of transmission of nerve impulse; • branching involved in salivary gland morphogenesis; • epithelial cell proliferation involved in salivary gland morphogenesis; • glucagon secretion; • interleukin-6-mediated signaling pathway; • cellular response to hydrogen peroxide; • positive regulation of ERK1 and ERK2 cascade; • negative regulation of neuron death; • positive regulation of STAT protein import into nucleus;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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　　[★]

英: cytokine receptor gp130

[pmid3294161-1] Ferguson-Smith AC, Chen YF, Newman MS, May LT, Sehgal PB, Ruddle FH (April 1988). "Regional localization of the interferon-beta 2/B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7p15-p21". Genomics 2 (3): 203–208. doi:10.1016/0888-7543(88)90003-1. PMID 3294161.

[2] van der Poll T, Keogh CV, Guirao X, Buurman WA, Kopf M, Lowry SF (1997). "Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia". J Infect Dis 176 (2): 439–444. doi:10.1086/514062. PMID 9237710.

[3] Febbraio MA, Pedersen BK (2005). "Contraction-induced myokine production and release: is skeletal muscle an endocrine organ?". Exerc Sport Sci Rev 33 (3): 114–119. doi:10.1097/00003677-200507000-00003. PMID 16006818.

[pmid15772055-4] Petersen AM, Pedersen BK (April 2005). "The anti-inflammatory effect of exercise". J. Appl. Physiol. 98 (4): 1154–1162. doi:10.1152/japplphysiol.00164.2004. PMID 15772055.

[pmid7845624-5] Banks WA, Kastin AJ, Gutierrez EG (September 1994). "Penetration of interleukin-6 across the murine blood–brain barrier". Neurosci. Lett. 179 (1–2): 53–6. doi:10.1016/0304-3940(94)90933-4. PMID 7845624.

[Bastard27041999-6] Bastard J, Jardel C, Delattre J, Hainque B et al. (1999). "Evidence for a Link Between Adipose Tissue Interleukin-6 Content and Serum C-Reactive Protein Concentrations in Obese Subjects". Circulation 99 (16): 2219–2222. doi:10.1161/01.CIR.99.16.2219.c.

[pmid19546306-7] Benedict C, Scheller J, Rose-John S, Born J, Marshall L (October 2009). "Enhancing influence of intranasal interleukin-6 on slow-wave activity and memory consolidation during sleep". FASEB J. 23 (10): 3629–3636. doi:10.1096/fj.08-122853. PMID 19546306.

[8] Heinrich PC, Behrmann, I, Müller-Newen G, Schaper F, Graeve L (1998). "Interleukin-6 type cytokine signalling through the gp130(Jak/STAT pathway". Biochem. J. 334 (Pt 2): 297–314. PMC 1219691. PMID 9716487.

[9] Kishimoto T, Akira S, Narazaki M, Taga T (1995). "Interleukin-6 family of cytokines and gp130". Blood 86 (4): 1243–54. PMID 7632928.

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cytokine receptor gp130