- Interleukin 1
Name = interleukin 1, alpha
caption = Crystal structure of IL-1a (PDB|2ILA).
width = 250
HGNCid = 5991
AltSymbols = IL1; IL-1A; IL1; IL1-ALPHA; IL1F1
EntrezGene = 3552
OMIM = 147760
RefSeq = NM_000575
UniProt = P01583
Chromosome = 2
Arm = q
Band = 12
LocusSupplementaryData = -q21protein
Name = Interleukin 1 beta
caption = Crystal structure of IL-1b (PDB|31BI).
width = 250
HGNCid = 5992
AltSymbols = , IL1F2
EntrezGene = 3553
OMIM = 147720
RefSeq = NM_000576
UniProt = P01584
PDB = 2MIB
Chromosome = 2
Arm = q
Band = 13-q21
LocusSupplementaryData = Interleukin-1 (IL-1) is one of the first
cytokines ever described. Its initial discovery was as a factor that could induce fever, control lymphocytes, increase the number of bone marrowcells and cause degeneration of bone joints. At this time, IL-1 was known under several other names including endogenous pyrogen, lymphocyte activating factor, haemopoetin-1 and mononuclear cell factor, amongst others. It was around 1984-1985 when scientists confirmed that IL-1 was actually composed of two distinct proteins, now called IL-1α and IL-1β.cite journal | author = Dinarello CA | title = The interleukin-1 family: 10 years of discovery | journal = FASEB J. | volume = 8 | issue = 15 | pages = 1314–25 | year = 1994 | pmid = 8001745 | doi = | issn = | url = http://www.fasebj.org/cgi/content/abstract/8/15/1314 ]
The Interleukin-1 superfamily
The original members of the IL-1 superfamily are IL-1α, IL-1β, and the
IL-1 Receptor antagonist(IL-1RA).
* IL-1α and -β are pro-inflammatory
cytokines involved in immune defense against infection.
* The IL-1RA is a molecule that competes for receptor binding with IL-1α and IL-1β, blocking their role in immune activation.
Recent years have seen the addition of other molecules to the IL-1 superfamily including
IL-18cite journal | author = Huising MO, Stet RJ, Savelkoul HF, Verburg-van Kemenade BM | title = The molecular evolution of the interleukin-1 family of cytokines; IL-18 in teleost fish | journal = Dev. Comp. Immunol. | volume = 28 | issue = 5 | pages = 395–413 | year = 2004 | pmid = 15062640 | doi = 10.1016/j.dci.2003.09.005 ] and six more genes with structural homology to IL-1α, IL-1β or IL-1RA. These latter six members are named Gene|IL1F5, Gene|IL1F6, Gene|IL1F7, Gene|IL1F8, Gene|IL1F9, and Gene|IL1F10. In accord, IL-1α, IL-1β, and IL-1RA have been renamed IL-1F1, IL-1F2, and IL-1F3, respectively.cite journal | author = Sims JE, Nicklin MJ, Bazan JF, Barton JL, Busfield SJ, Ford JE, Kastelein RA, Kumar S, Lin H, Mulero JJ, Pan J, Pan Y, Smith DE, Young PR | title = A new nomenclature for IL-1-family genes | journal = Trends Immunol. | volume = 22 | issue = 10 | pages = 536–7 | year = 2001 | pmid = 11574262 | doi = 10.1016/S1471-4906(01)02040-3 ] cite journal | author = Dunn E, Sims JE, Nicklin MJ, O'Neill LA | title = Annotating genes with potential roles in the immune system: six new members of the IL-1 family | journal = Trends Immunol. | volume = 22 | issue = 10 | pages = 533–6 | year = 2001 | pmid = 11574261 | doi = 10.1016/S1471-4906(01)02034-8 ]
A further putative member of the IL-1 family has been recently described that is called IL-33 or IL-1F11, although this name is not officially accepted in the HGNC gene family nomenclature database. [ [http://www.genenames.org/ HGNC Home Page ] ]
IL-1α and IL-1β
Both IL-1α and IL-1β are produced by
macrophages, monocytes and dendritic cells. They form an important part of the inflammatory response of the body against infection. These cytokines increase the expression of adhesion factors on endothelialcells to enable transmigration of leukocytes, the cells that fight pathogens, to sites of infection and re-set the hypothalamusthermoregulatory center, leading to an increased body temperature which expresses itself as fever. IL-1 is therefore called an endogenous pyrogen. The increased body temperature helps the body's immune system to fight infection. IL-1 is also important in the regulation of hematopoiesis. IL-1β production in peripheral tissue has also been associated with hyperalgesia(increased sensitivity to pain) associated with fever.cite journal | author = Morgan MM, Clayton CC, Heinricher MM | title = Dissociation of hyperalgesia from fever following intracerebroventricular administration of interleukin-1beta in the rat | journal = Brain Res. | volume = 1022 | issue = 1-2 | pages = 96–100 | year = 2004 | pmid = 15353218 | doi = 10.1016/j.brainres.2004.06.063 ]
For the most part, these two forms of IL-1 bind to the same cellular receptor. This receptor is composed of two related, but non-identical, subunits that transmit intracellular signals via a pathway that is mostly shared with certain other receptors. These include the Toll family of innate immune receptors and the receptor for IL-18.
IL-1α is a pleiotropic cytokine involved in various
immune responses, inflammatory processes, and hematopoiesis. This cytokine is produced by many cell types but is only secreted by monocytesand macrophages. It is produced as a proprotein, which is proteolyticallyprocessed by calpainand released in a mechanism that is still not well studied. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. It has been suggested that the polymorphism of these genes is associated with rheumatoid arthritisand Alzheimer's disease.
tructure of the IL-1 superfamily
IL-1α and IL-1β are produced as precursor peptides. In other words they are made as a long protein that is then processed to release a shorter, active molecule, which is called the mature protein. Mature IL-1β, for instance, is released from Pro-IL-1β following cleavage by a certain member of the
caspasefamily of proteins, called caspase-1or the interleukin-1 converting enzyme(ICE). The 3-dimensional structure of the mature forms of each member of the human IL-1 superfamily is composed of 12-14 β-strands producing a barrel-shaped protein.
The receptors for interleukin 1 are:
Interleukin 1 receptor, type I
Interleukin 1 receptor, type II
*cite journal | author=Verweij CL, Bayley JP, Bakker A, Kaijzel EL |title=Allele specific regulation of cytokine genes: monoallelic expression of the IL-1A gene |journal=Adv. Exp. Med. Biol. |volume=495 |issue= |pages= 129–39 |year= 2002 |pmid= 11774556 |doi=
*cite journal | author=Griffin WS, Mrak RE |title=Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer's disease |journal=J. Leukoc. Biol. |volume=72 |issue= 2 |pages= 233–8 |year= 2002 |pmid= 12149413 |doi=
*cite journal | author=Arend WP |title=The balance between IL-1 and IL-1Ra in disease |journal=Cytokine Growth Factor Rev. |volume=13 |issue= 4-5 |pages= 323–40 |year= 2003 |pmid= 12220547 |doi=
*cite journal | author=Copeland KF |title=Modulation of HIV-1 transcription by cytokines and chemokines |journal=Mini reviews in medicinal chemistry |volume=5 |issue= 12 |pages= 1093–101 |year= 2006 |pmid= 16375755 |doi=
*cite journal | author=Schmidt DR, Kao WJ |title=The interrelated role of fibronectin and interleukin-1 in biomaterial-modulated macrophage function |journal=Biomaterials |volume=28 |issue= 3 |pages= 371–82 |year= 2007 |pmid= 16978691 |doi= 10.1016/j.biomaterials.2006.08.041
*cite journal | author=Huynh-Ba G, Lang NP, Tonetti MS, Salvi GE |title=The association of the composite IL-1 genotype with periodontitis progression and/or treatment outcomes: a systematic review |journal=J. Clin. Periodontol. |volume=34 |issue= 4 |pages= 305–17 |year= 2007 |pmid= 17378887 |doi= 10.1111/j.1600-051X.2007.01055.x
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