Interleukin 1 receptor antagonist
Encyclopedia
The interleukin-1 receptor antagonist (IL-1RA) is a protein
that in humans is encoded by the IL1RN gene
.
IL-1RA was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories. IL-1RA, is an agent that binds non-productively to the cell surface interleukin-1 receptor
(IL-1R). IL-1R is the same receptor that binds interleukin 1 (IL-1). Hence IL-1RA prevents IL-1 from sending a signal to that cell.
family. IL1Ra 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. . 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.
Mutations in the IL1RN gene results in a rare disease
called deficiency of the interleukin-1–receptor antagonist
(DIRA). Variants of the IL1RN gene is also associated with risk of schizophrenia. Elevated levels of IL1RN has been found in serum of schizophrenia patients.
An interleukin 1 receptor antagonist is used in the treatment of rheumatoid arthritis
, an autoimmune disease in which IL-1 plays a key role. It is commercially produced as anakinra
, which is a human recombinant
form of IL-1RA. In terms of protein similarities, IL-1β is more closely related to IL-1RA than it is to IL- 1α. The amino acids that are identical between mature human IL-1α and mature IL-1β is 22% while it is 26% when comparing IL-1β to IL-1RA and only 18% when comparing IL-1α to IL-1RA.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the IL1RN gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
IL-1RA was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories. IL-1RA, is an agent that binds non-productively to the cell surface interleukin-1 receptor
Interleukin-1 receptor
Interleukin-1 receptor is a cytokine receptor which binds interleukin 1. Two forms of the receptor exist. The type I receptor is primarily responsible for transmitting the inflammatory effects of interleukin-1 while type II receptors may act as a suppressor of IL-1 activity by competing for...
(IL-1R). IL-1R is the same receptor that binds interleukin 1 (IL-1). Hence IL-1RA prevents IL-1 from sending a signal to that cell.
Function
IL-1RA is a member of the interleukin 1 cytokineCytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
family. IL1Ra 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. . This protein inhibits the activities of interleukin 1, alpha (IL1A
IL1A
Interleukin-1 alpha is a protein that in humans is encoded by the IL1A gene.The protein encoded by this gene is a cytokine of the interleukin-1 family. Interleukin-1 alpha possesses a wide spectrum of metabolic, physiological, haematopoietic activities, and plays one of the central roles in the...
) and interleukin 1, beta (IL1B
IL1B
Interleukin-1 beta also known as catabolin, is a cytokine protein that in humans is encoded by the IL1B gene. IL-1β precursor is cleaved by caspase 1 . Cytosolic thiol protease cleaves the product to form mature IL-1β.- Function :Interleukin 1 was discovered by Gery in 1972...
), 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.
Clinical significance
A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer.Mutations in the IL1RN gene results in a rare disease
Rare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
called deficiency of the interleukin-1–receptor antagonist
Deficiency of the interleukin-1–receptor antagonist
Deficiency of the interleukin-1–receptor antagonist is a rare, autosomal recessive, genetic autoinflammatory syndrome resulting from mutations in IL1RN, the gene encoding the interleukin 1 receptor antagonist....
(DIRA). Variants of the IL1RN gene is also associated with risk of schizophrenia. Elevated levels of IL1RN has been found in serum of schizophrenia patients.
An interleukin 1 receptor antagonist is used in the treatment of rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, an autoimmune disease in which IL-1 plays a key role. It is commercially produced as anakinra
Anakinra
Anakinra is a drug used to treat rheumatoid arthritis.-Mechanism:Anakinra is an interleukin-1 receptor antagonist...
, which is a human recombinant
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
form of IL-1RA. In terms of protein similarities, IL-1β is more closely related to IL-1RA than it is to IL- 1α. The amino acids that are identical between mature human IL-1α and mature IL-1β is 22% while it is 26% when comparing IL-1β to IL-1RA and only 18% when comparing IL-1α to IL-1RA.