Interleukin-1 receptor antagonist

IL1RN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ILR, 1ILT, 1IRA, 1IRP, 2IRT
Identifiers
Aliases	IL1RN, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3, IL1F3, IL1RA, IRAP, MVCD4, interleukin 1 receptor antagonist
External IDs	OMIM: 147679; MGI: 96547; HomoloGene: 11163; GeneCards: IL1RN; OMA:IL1RN - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q14.1 Start 113,099,315 bp[1] End 113,134,016 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 A3|2 16.36 cM Start 24,226,865 bp[2] End 24,241,506 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in palpebral conjunctiva gums oral cavity body of tongue periodontal fiber amniotic fluid skin of abdomen pancreatic ductal cell human penis blood Top expressed in lip esophagus left colon skin of back skin of abdomen conjunctival fornix blood corneal stroma epidermis liver More reference expression data BioGPS More reference expression data
Gene ontology Molecular function interleukin-1 type I receptor antagonist activity interleukin-1, type II receptor binding protein binding interleukin-1, type I receptor binding interleukin-1 type II receptor antagonist activity interleukin-1 receptor binding cytokine activity interleukin-1 receptor antagonist activity Cellular component cytoplasm vesicle plasma membrane intracellular anatomical structure extracellular region extracellular exosome extracellular space Biological process negative regulation of interleukin-1-mediated signaling pathway lipid metabolism response to glucocorticoid insulin secretion acute-phase response negative regulation of heterotypic cell-cell adhesion negative regulation of cytokine-mediated signaling pathway inflammatory response immune response fever generation regulation of signaling receptor activity cytokine-mediated signaling pathway neutrophil chemotaxis positive regulation of interleukin-6 production positive regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of JNK cascade interleukin-1-mediated signaling pathway cellular response to lipopolysaccharide Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3557 16181 Ensembl ENSG00000136689 ENSMUSG00000026981 UniProt P18510 P25085 RefSeq (mRNA) NM_000577 NM_173841 NM_173842 NM_173843 NM_001318914 NM_001379360 NM_001039701 NM_001159562 NM_031167 RefSeq (protein) NP_000568 NP_001305843 NP_776213 NP_776214 NP_776215 NP_001366289 NP_001034790 NP_001153034 NP_112444 Location (UCSC) Chr 2: 113.1 – 113.13 Mb Chr 2: 24.23 – 24.24 Mb PubMed search [3] [4]
Wikidata
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The interleukin-1 receptor antagonist (IL-1RA) is a protein that in humans is encoded by the IL1RN gene.^[5][6]

IL-1RA was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories.^[7] IL-1RA is an agent that binds non-productively to the cell surface interleukin-1 receptor (IL-1R), the same receptor that binds interleukin 1 family (IL-1), preventing IL-1's from sending a signal to that cell.

Function

IL-1RA is a member of the interleukin 1 cytokine family. IL-1RA is secreted by various types of cells including immune cells, epithelial cells, and adipocytes, and is a natural inhibitor of the pro-inflammatory effect of IL1β.^[8] This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.^[9]

Clinical significance

A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures^[10] and gastric cancer.^[11]

Biallelic deleterious mutations in the IL1RN gene results in a rare autoinflammatory disease called deficiency of the interleukin-1–receptor antagonist (DIRA).^[12] Variants of the IL1RN gene is also associated with risk of schizophrenia.^[13][14] Elevated levels of IL-1RA has been found in serum of schizophrenia patients.^[15]

In treatment of temporomandibular joint osteoarthritis (TMJOA) the messenger RNA (mRNA) of IL-1RA can be used. The IL-1RA mRNA reduces pain and joint inflammation by blocking inflammatory cascade signals that lead to osteoarthritis progression.^[16]

A recombinant, slightly modified version of interleukin 1 receptor antagonist called anakinra is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role.^[17] Anakinra differs from native human IL-1RA in that it has the addition of a single methionine residue at its amino terminus ^[18]

The cytoplasmic and secreted isoforms of IL-1RA can suppress tumors such as squamous cell carcinoma. The cytoplasmic isoform can protect epithelial cells from environmental factors and compete with IL1A in binding with receptors preventing activation. Then, the secreted isoform regulates IL1B in tumor microenvironments by inhibiting glycolysis of IL1B and proliferation of tumor cells, thus preventing the movement of tumor cells.^[19]

Use in horses

Interleukin 1 receptor antagonist is used in horses for the treatment of equine lameness secondary to joint and soft-tissue injury. IL-1RA obstructs the IL1B inflammatory cascade rather than helping to restore damaged tissue.^[20]

References

Further reading

External links

• Interleukin+1+Receptor+Antagonist+Protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)