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Interleukin 6 (interferon, beta 2)
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| PDB rendering based on 1ALU. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography | ||
| Available structures: 1alu, 1il6, 1p9m, 2il6 | ||
| Identifiers | ||
| Symbol(s) | IL6; HGF; BSF2; HSF; IFNB2; IL-6 | |
| External IDs | OMIM: 147620 MGI: 96559 HomoloGene: 502 | |
| RNA expression pattern | ||
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| Orthologs | ||
| Human | Mouse | |
| Entrez | 3569 | 16193 |
| Ensembl | ENSG00000136244 | ENSMUSG00000025746 |
| Uniprot | P05231 | Q0PMN1 |
| Refseq | NM_000600 (mRNA) NP_000591 (protein) |
NM_031168 (mRNA) NP_112445 (protein) |
| Location | Chr 7: 22.73 - 22.74 Mb | Chr 5: 30.34 - 30.35 Mb |
| Pubmed search | [1] | [2] |
Interleukin-6 (IL-6) is an interleukin, acts as both a pro-inflammatory and anti-inflammatory cytokine. The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mouse Genome Informatics (MGI website is run by The Jackson Laboratory. HomoloGene, a tool of the National Center for Biotechnology Information (NCBI is a system for automated detection of homologs (similarity attributable to descent The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences Ensembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent UniProt is the uni versal prot ein resource a central repository of Protein data created by combining Swiss-Prot, TrEMBL PubMed is a free search engine for accessing the MEDLINE database of citations and abstracts of biomedical research articles Interleukins are a group of Cytokines (secreted Signaling molecules) that were first seen to be expressed by White blood cells ( Leukocytes hence Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular It is secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that In terms of host response to a foreign pathogen, IL-6 has been shown, in mice, to be required for resistance against the bacterium, Streptococcus pneumoniae[1]. Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, alpha-hemolytic diplococcus aerotolerant anaerobe and a member of the Genus IL-6 is also a "myokine," a cytokine produced from muscle, and is elevated in response to muscle contraction[2]. 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 (Petersen, J Appl Physiol 2005). Additionally, osteoblasts secrete IL-6 to stimulate osteoclast formation. An osteoblast (from the Greek words for " Bone " and "germ" or embryonic is a mononucleate cell that is responsible for bone formation An osteoclast (from the Greek words for "bone" and "broken" is a type of Bone cell that removes Bone tissue by removing its Mineralized matrix Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. Smooth muscle is a type of non- Striated muscle, found within the Tunica media layer of large and small Arteries and Veins, the bladder The tunica media (or just media) ( middle coat) is the middle layer of an Artery or Vein. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular 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.
Contents |
Functions of IL-6
IL-6 is one of the most important mediators of fever and of the acute phase response. Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris Acute-phase proteins are a class of Proteins whose plasma concentrations increase (positive acute phase proteins or decrease (negative acute phase proteins in response to In the 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). Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious Pathogen-associated molecular patterns, or PAMP s are small molecular motifs consistently found on Pathogens They are recognized by Toll-like receptors and These PAMPs bind to highly important detection molecules of the innate immune system, called Toll-like receptors (TLRs), that are present on the cell surface (or in intracellular compartments) which induce intracellular signaling cascades that give rise to inflammatory cytokine production. Immune system|Adaptive immune systemThe innate immune system comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner Toll-like receptors ( TLRs) are a class of single membrane-spanning non-catalytic receptors that recognize structurally conserved molecules derived from Microbes IL-6 is also essential for hybridoma growth and is found in many supplemental cloning media such as briclone. Hybridoma are cells that have been engineered to produce a desired Antibody in large amounts Briclone is an IL-6 enriched Cloning medium for use in the stages following fusion in Hybridoma production Inhibitors of IL-6 (including estrogen) are used to treat postmenopausal osteoporosis. Estrogens (US otherwise oestrogens or œstrogens) are a group of Steroid compounds named for their importance in the Estrous cycle, Osteoporosis is a Disease of Bone that leads to an increased risk of fracture.
The IL-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). Type I cytokine receptors are Transmembrane receptors expressed on the surface of cells that recognize and respond to Cytokines with four α-helical strands The cluster of differentiation (often abbreviated as CD) is a protocol used for the identification and investigation of Cell surface molecules present on Leukocytes Glycoprotein 130 (also known as gp130, IL6ST, IL6-beta or CD130) is a Transmembrane protein which is the founding member of the class 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. Leukemia inhibitory factor, or LIF, an Interleukin 6 class Cytokine, is a chemical in cells that affects their growth and development Ciliary neurotrophic factor, also known as CNTF, is a human Gene. Oncostatin M ( OSM) is a pleitropic Cytokine that belongs to the Interleukin 6 group of cytokines Interleukin 11 (IL-11 is a multifunctional Cytokine first isolated in 1990 from Bone marrow -derived stromal cells Cardiotrophin-1 (CT-1 is a Cytokine. It is a cardiac hypertrophic factor of 21 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). Not to be confused with Intercellular, meaning "between cells" In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences Janus kinase ( JAK) is a family of intracellular non-receptor Tyrosine kinases that transduce Cytokine -mediated signals via the JAK-STAT pathway
IL-6 is probably the best studied of the cytokines that use gp130 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 herpes virus interleukin 6 like protein (KSHV-IL6). Interleukin 11 (IL-11 is a multifunctional Cytokine first isolated in 1990 from Bone marrow -derived stromal cells Overview Interleukin-27 (IL-27 is a Heterodimeric Cytokine belonging to the IL-12 family that is composed of two subunits Epstein-Barr Ciliary neurotrophic factor, also known as CNTF, is a human Gene. Cardiotrophin-1 (CT-1 is a Cytokine. It is a cardiac hypertrophic factor of 21 Leukemia inhibitory factor, or LIF, an Interleukin 6 class Cytokine, is a chemical in cells that affects their growth and development Oncostatin M ( OSM) is a pleitropic Cytokine that belongs to the Interleukin 6 group of cytokines Kaposi's sarcoma (KS is a tumor caused by Human herpesvirus 8 ( HHV8) also known as Kaposi's sarcoma-associated herpesvirus (KSHV [3] These cytokines are commonly referred to as the IL-6 like or gp130 utilising cytokines.
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.
References
- ^ 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): 439-44. 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): 114-9. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16006818.
- ^ Kishimoto T, Akira S, Narazaki M, Taga T (1995). "Interleukin-6 family of cytokines and gp130". Blood 86: 1243-1254.
Further reading
- De Kloet ER, Oitzl MS, Schöbitz B (1994). "Cytokines and the brain corticosteroid receptor balance: relevance to pathophysiology of neuroendocrine-immune communication. ". Psychoneuroendocrinology 19 (2): 121-34. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 8190832.
- Morishita R, Aoki M, Yo Y, Ogihara T (2003). "Hepatocyte growth factor as cardiovascular hormone: role of HGF in the pathogenesis of cardiovascular disease. ". Endocr. J. 49 (3): 273-84. PMID 12201209.
- Ishihara K, Hirano T (2003). "IL-6 in autoimmune disease and chronic inflammatory proliferative disease. ". Cytokine Growth Factor Rev. 13 (4-5): 357-68. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12220549.
- Culig Z, Bartsch G, Hobisch A (2003). "Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth. ". Mol. Cell. Endocrinol. 197 (1-2): 231-8. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12431817.
- Rattazzi M, Puato M, Faggin E, et al. (2004). "C-reactive protein and interleukin-6 in vascular disease: culprits or passive bystanders?". J. Hypertens. 21 (10): 1787-803. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 14508181.
- Tackey E, Lipsky PE, Illei GG (2005). "Rationale for interleukin-6 blockade in systemic lupus erythematosus. ". Lupus 13 (5): 339-43. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15230289.
- Berger FG (2005). "The interleukin-6 gene: a susceptibility factor that may contribute to racial and ethnic disparities in breast cancer mortality. ". Breast Cancer Res. Treat. 88 (3): 281-5. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15609131.
- Stenvinkel P, Ketteler M, Johnson RJ, et al. (2005). "IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia--the good, the bad, and the ugly. ". Kidney Int. 67 (4): 1216-33. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15780075.
- Vgontzas AN, Bixler EO, Lin HM, et al. (2005). "IL-6 and its circadian secretion in humans. ". Neuroimmunomodulation 12 (3): 131-40. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15905620.
- Jones SA (2005). "Directing transition from innate to acquired immunity: defining a role for IL-6. ". J. Immunol. 175 (6): 3463-8. PMID 16148087.
- Kristiansen OP, Mandrup-Poulsen T (2006). "Interleukin-6 and diabetes: the good, the bad, or the indifferent?". Diabetes 54 Suppl 2: S114-24. PMID 16306329.
- Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines. ". Mini reviews in medicinal chemistry 5 (12): 1093-101. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16375755.
- Mastorakos G, Ilias I (2007). "Interleukin-6: a cytokine and/or a major modulator of the response to somatic stress. ". Ann. N. Y. Acad. Sci. 1088: 373-81. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17192581.
- Dubiński A, Zdrojewicz Z (2007). "[The role of interleukin-6 in development and progression of atherosclerosis]". Pol. Merkur. Lekarski 22 (130): 291-4. PMID 17684929.
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