Interleukin 1 beta

Interleukin 1 beta
PDB rendering based on 31bi.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1HIB​, 1I1B​, 1IOB​, 1ITB​, 1L2H​, 1S0L​, 1T4Q​, 1TOO​, 1TP0​, 1TWE​, 1TWM​, 21BI​, 2I1B​, 2KH2​, 2NVH​, 31BI​, 3LTQ​, 3O4O​, 3POK​, 41BI​, 4DEP​, 4G6J​, 4G6M​, 4GAF​, 4GAI​, 4I1B​, 5I1B​, 6I1B​, 7I1B​, 9ILB​
Identifiers
Symbols	IL1B ; IL-1; IL1-BETA; IL1F2
External IDs	OMIM: 147720 MGI: 96543 HomoloGene: 481 GeneCards: IL1B Gene
Gene ontology Molecular function • cytokine activity • interleukin-1 receptor binding • protein domain specific binding Cellular component • extracellular region • extracellular space • cytosol • secretory granule Biological process • negative regulation of transcription from RNA polymerase II promoter • MAPK cascade • activation of MAPK activity • fever generation • response to hypoxia • positive regulation of protein phosphorylation • stimulatory C-type lectin receptor signaling pathway • inflammatory response to antigenic stimulus • chronic inflammatory response to antigenic stimulus • positive regulation of T cell mediated immunity • purine nucleobase metabolic process • apoptotic process • inflammatory response • signal transduction • positive regulation of cytosolic calcium ion concentration • cell-cell signaling • embryo implantation • aging • memory • estrogen metabolic process • negative regulation of cell proliferation • glycoprotein metabolic process • response to heat • response to ozone • response to gamma radiation • positive regulation of vascular endothelial growth factor production • positive regulation of gene expression • negative regulation of glucose transport • negative regulation of glutamate secretion • smooth muscle adaptation • cytokine-mediated signaling pathway • pentacyclic triterpenoid metabolic process • hyaluronan biosynthetic process • neutrophil chemotaxis • polyketide metabolic process • ovulation • sequestering of triglyceride • positive regulation of vascular endothelial growth factor receptor signaling pathway • positive regulation of fever generation • lipopolysaccharide-mediated signaling pathway • positive regulation of prostaglandin secretion • response to estradiol • interleukin-1 beta production • positive regulation of granulocyte macrophage colony-stimulating factor production • positive regulation of interferon-gamma production • positive regulation of interleukin-6 production • positive regulation of interleukin-8 production • positive regulation of immature T cell proliferation in thymus • positive regulation of histone phosphorylation • response to ATP • response to vitamin D • response to L-ascorbic acid • positive regulation of heterotypic cell-cell adhesion • positive regulation of histone acetylation • social behavior • ectopic germ cell programmed cell death • positive regulation of myosin light chain kinase activity • response to stilbenoid • cellular response to drug • response to diuretic • response to statin • wound healing • positive regulation of T cell proliferation • positive regulation of NF-kappaB import into nucleus • positive regulation of apoptotic process • regulation of I-kappaB kinase/NF-kappaB signaling • response to morphine • negative regulation of MAP kinase activity • response to peptide hormone • protein kinase B signaling • positive regulation of JUN kinase activity • positive regulation of chemokine biosynthetic process • positive regulation of interleukin-2 biosynthetic process • innate immune response • positive regulation of interleukin-6 biosynthetic process • positive regulation of nitric oxide biosynthetic process • response to ethanol • negative regulation of neuron differentiation • positive regulation of angiogenesis • negative regulation of lipid metabolic process • positive regulation of mitotic nuclear division • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • negative regulation of insulin receptor signaling pathway • positive regulation of protein export from nucleus • positive regulation of astrocyte differentiation • positive regulation of phagocytosis • regulation of insulin secretion • negative regulation of lipid catabolic process • positive regulation of lipid catabolic process • positive regulation of membrane protein ectodomain proteolysis • positive regulation of sequence-specific DNA binding transcription factor activity • positive regulation of NF-kappaB transcription factor activity • positive regulation of cell adhesion molecule production • positive regulation of calcidiol 1-monooxygenase activity • negative regulation of adiponectin secretion • positive regulation of ERK1 and ERK2 cascade • monocyte aggregation • cellular response to antibiotic • cellular response to mechanical stimulus • cellular response to organic substance • cellular response to glucose stimulus • cellular response to fatty acid • cellular response to organic cyclic compound • cellular response to methotrexate • response to dexamethasone • positive regulation of monocyte chemotactic protein-1 production • positive regulation of neutrophil chemotaxis • extrinsic apoptotic signaling pathway in absence of ligand • negative regulation of branching morphogenesis of a nerve • negative regulation of neural precursor cell proliferation • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3553	16176
Ensembl	ENSG00000125538	ENSMUSG00000027398
UniProt	P01584	P10749
RefSeq (mRNA)	NM_000576	NM_008361
RefSeq (protein)	NP_000567	NP_032387
Location (UCSC)	Chr 2: 112.83 – 112.84 Mb	Chr 2: 129.36 – 129.37 Mb
PubMed search

Interleukin 1 beta (IL1β) also known as '"leukocytic pyrogen"', "'leukocytic endogenous mediator'", "'mononuclear cell factor'", "'lymphocyte activating factor'" and other names, is a cytokine protein that in humans is encoded by the IL1B gene.^[1][2][3][4] There are two genes for Interleukin-1 (IL-1): IL-1 alpha and IL-1 beta (this gene). IL-1β precursor is cleaved by cytosolic caspase 1 (interleukin 1 beta convertase) to form mature IL-1β.

Function

The fever-producing property of human leukocytic pyrogen (Interleukin 1) was purified by Dinarello in 1977 (PNAS) with a specific activity of 10-20 nanograms/kg. In 1979, Dinarello reported that purified human leukocytic pyrogen was the same molecule that was described by Igal Gery in 1972.^[5][6][7] He named it lymphocyte-activating factor (LAF) because it was a lymphocyte mitogen. It was not until 1984 that interleukin 1 was discovered to consist of two distinct proteins, now called interleukin-1 alpha and interleukin-1 beta.^[2]

IL-1β is a member of the interleukin 1 family of cytokines. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2.^[8]

Properties

The molecular weight of the proteolytically processed IL1B is 17.5 kDa. IL1B has the following amino acid sequence:

• APVRSLNCTL RDSQQKSLVM SGPYELKALH LQGQDMEQQV VFSMSFVQGE ESNDKIPVAL GLKEKNLYLS CVLKDDKPTL QLESVDPKNY PKKKMEKRFV FNKIEINNKL EFESAQFPNW YISTSQAENM PVFLGGTKGG QDITDFTMQF VSS

The physiological activity determined from the dose dependent proliferation of murine D10S cells is 2.5 x 10⁸ to 7.1 x 10⁸ units/mg.

Clinical significance

Increased production of IL-1B causes a number of different autoinflammatory syndromes, most notably the monogenic conditions referred to as CAPS, due to mutations in the inflammasome receptor NLRP3 which triggers processing of IL-1B.^[9]

Therapies targeting interleukin 1 beta

Canakinumab is a human monoclonal antibody targeted at IL-1B, and approved in many countries for treatment of cryopyrin-associated periodic syndromes.

Orthographic note

Because many authors of scientific manuscripts make the minor error of using a homoglyph, sharp s (ß), instead of beta (β), mentions of "IL-1ß" [sic] often become "IL-1ss" [sic] upon automated transcoding (because ß transcodes to ss). This is why so many mentions of the latter appear in web search results.

See also

• Interleukin 1

References

1. Auron PE, Webb AC, Rosenwasser LJ, Mucci SF, Rich A, Wolff SM, Dinarello CA (1984). "Nucleotide sequence of human monocyte interleukin 1 precursor cDNA". Proc. Natl. Acad. Sci. U.S.A. 81 (24): 7907–11. doi:10.1073/pnas.81.24.7907. PMC 392262. PMID 6083565.
2. "Catabolin" is the name given by Jeremy Saklatvala for IL-1 alpha. March CJ, Mosley B, Larsen A, Cerretti DP, Braedt G, Price V, Gillis S, Henney CS, Kronheim SR, Grabstein K (1985). "Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs". Nature 315 (6021): 641–7. doi:10.1038/315641a0. PMID 2989698.
3. Clark BD, Collins KL, Gandy MS, Webb AC, Auron PE (1986). "Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene". Nucleic Acids Res 14 (20): 7897–1914. doi:10.1093/nar/14.20.7897. PMID 3490654.
4. Bensi G, Raugei G, Palla E, Carinci V, Tornese Buonamassa D, Melli M (1987). "Human interleukin-1 beta gene". Gene 52 (1): 95–101. doi:10.1016/0378-1119(87)90398-2. PMID 2954882.
5. Gery I, Gershon RK, Waksman BH (1972). "Potentiation of the T-lymphocyte response to mitogens. I. The responding cell". J. Exp. Med. 136 (1): 128–142. doi:10.1084/jem.136.1.128. PMC 2139184. PMID 5033417.
6. Gery I, Waksman BH (1972). "Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s)". J. Exp. Med. 136 (1): 143–155. doi:10.1084/jem.136.1.143. PMC 2139186. PMID 5033418.
7. Gery I, Handschumacher RE (1974). "Potentiation of the T lymphocyte response to mitogens. III. Properties of the mediator(s) from adherent cells". Cell. Immunol. 11 (1-3): 162–9. doi:10.1016/0008-8749(74)90016-1. PMID 4549027.
8. "Entrez Gene: IL1B interleukin 1, beta".
9. Masters SL, Simon A, Aksentijevich I, Kastner DL (2009). "Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*)". Annu. Rev. Immunol. 27: 621–68. doi:10.1146/annurev.immunol.25.022106.141627. PMC 2996236. PMID 19302049.

Further reading

• Smirnova MG, Kiselev SL, Gnuchev NV, Birchall JP, Pearson JP (2003). "Role of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and interleukin-8 in the pathogenesis of the otitis media with effusion". Eur. Cytokine Netw. 13 (2): 161–72. PMID 12101072.
• Griffin WS, Mrak RE (2002). "Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer's disease". J. Leukoc. Biol. 72 (2): 233–8. PMID 12149413.
• Arend WP (2003). "The balance between IL-1 and IL-1Ra in disease". Cytokine Growth Factor Rev. 13 (4-5): 323–40. doi:10.1016/S1359-6101(02)00020-5. PMID 12220547.
• Chakravorty M, Ghosh A, Choudhury A, Santra A, Hembrum J, Roychoudhury S (2004). "Ethnic differences in allele distribution for the IL8 and IL1B genes in populations from eastern India". Hum. Biol. 76 (1): 153–9. doi:10.1353/hub.2004.0016. PMID 15222686.
• Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.
• Maruyama Y, Stenvinkel P, Lindholm B (2005). "Role of interleukin-1beta in the development of malnutrition in chronic renal failure patients". Blood Purif. 23 (4): 275–81. doi:10.1159/000086012. PMID 15925866.
• Roy D, Sarkar S, Felty Q (2006). "Levels of IL-1 beta control stimulatory/inhibitory growth of cancer cells". Front. Biosci. 11: 889–98. doi:10.2741/1845. PMID 16146780.
• Copeland KF (2005). "Modulation of HIV-1 transcription by cytokines and chemokines". Mini Rev Med Chem 5 (12): 1093–101. doi:10.2174/138955705774933383. PMID 16375755.
• Prinz C, Schwendy S, Voland P (2006). "H pylori and gastric cancer: shifting the global burden". World J. Gastroenterol. 12 (34): 5458–64. PMID 17006981.
• Kamangar F, Cheng C, Abnet CC, Rabkin CS (2006). "Interleukin-1B polymorphisms and gastric cancer risk--a meta-analysis". Cancer Epidemiol. Biomarkers Prev. 15 (10): 1920–8. doi:10.1158/1055-9965.EPI-06-0267. PMID 17035400.

External links

• IL1B protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.