IL1B
Encyclopedia
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 (interleukin 1 beta convertase). Cytosolic thiol protease cleaves the product to form mature IL-1β.
IL-1β is a member of the interleukin 1 cytokine
family. 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.
IL1B has the following amino acid sequence:
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.
.
In one study of Korea
n population, two polymorphisms of the gene (rs16944 and rs1143627) were found to be associated with keratoconus
.
is a human monoclonal antibody targeted at IL-1B, and approved in many countries for treatment of cryopyrin-associated periodic syndrome
s.
Cytokine
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...
protein
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 IL1B 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-1β precursor is cleaved by caspase 1 (interleukin 1 beta convertase). Cytosolic thiol protease cleaves the product to form mature IL-1β.
Function
Interleukin 1 was discovered by Gery in 1972. He named it lymphocyte-activating factor (LAF) because it was a lymphocyte mitogen. It was not until 1985 that interleukin 1 was discovered to consist of two distinct proteins, now called interleukin-1 alpha and interleukin-1 beta.IL-1β is a member of the interleukin 1 cytokine
Cytokine
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. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1
Caspase 1
Caspase 1 is an enzyme that proteolytically cleaves other proteins, such as the precursor forms of the inflammatory cytokines interleukin 1-β and interleukin 18, into active mature peptides...
(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
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. The induction of cyclooxygenase-2
PTGS2
Prostaglandin-endoperoxide synthase 2, also known as cyclooxygenase-2 or simply COX-2, is an enzyme that in humans is encoded by the PTGS2 gene.- History :...
(PTGS2/COX2) by this cytokine in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS) is found to contribute to inflammatory pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
hypersensitivity. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2.
Properties
Mol 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
A number of studies associate the gene with susceptibility to schizophreniaSchizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
In one study of Korea
Korea
Korea ) is an East Asian geographic region that is currently divided into two separate sovereign states — North Korea and South Korea. Located on the Korean Peninsula, Korea is bordered by the People's Republic of China to the northwest, Russia to the northeast, and is separated from Japan to the...
n population, two polymorphisms of the gene (rs16944 and rs1143627) were found to be associated with keratoconus
Keratoconus
Keratoconus , is a degenerative disorder of the eye in which structural changes within the cornea cause it to thin and change to a more conical shape than its normal gradual curve....
.
Therapies that target it
CanakinumabCanakinumab
Canakinumab is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha....
is a human monoclonal antibody targeted at IL-1B, and approved in many countries for treatment of cryopyrin-associated periodic syndrome
Cryopyrin-associated periodic syndrome
Cryopyrin-associated periodic syndrome is a spectrum of autoinflammatory syndromes including familial cold autoinflammatory syndrome , the Muckle-Wells syndrome , and neonatal-onset multisystem inflammatory disease...
s.