Interleukin 1: Wikis

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interleukin 1, alpha
2ILA.png
Crystal structure of IL-1a (PDB 2ILA).
Identifiers
Symbol IL1A
Alt. symbols IL1; IL-1A; IL1; IL1-ALPHA; IL1F1
Entrez 3552
HUGO 5991
OMIM 147760
RefSeq NM_000575
UniProt P01583
Other data
Locus Chr. 2 q12-q21
Interleukin 1 beta
31BI.png
Crystal structure of IL-1b (PDB 31BI).
Identifiers
Symbol IL1B
Alt. symbols IL-1B; IL1-BETA; IL1F2
Entrez 3553
HUGO 5992
OMIM 147720
PDB 2MIB
RefSeq NM_000576
UniProt P01584
Other data
Locus Chr. 2 q13-q21

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 marrow cells 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.[1]

Contents

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-18[2] and six more genes with structural homology to IL-1α, IL-1β or IL-1RA. These latter six members are named IL1F5, IL1F6, IL1F7, IL1F8, IL1F9, and IL1F10. In accord, IL-1α, IL-1β, and IL-1RA have been renamed IL-1F1, IL-1F2, and IL-1F3, respectively.[3][4]

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.[5]

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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 endothelial cells to enable transmigration of leukocytes, the cells that fight pathogens, to sites of infection and re-set the hypothalamus thermoregulatory 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.[6]

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 monocytes and macrophages. It is produced as a proprotein, which is proteolytically processed by calpain and 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 arthritis and Alzheimer's disease.

Additionally IL-1α is essential for maintenance of skin barrier function, especially with increasing age.[7]

Structure 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 caspase family of proteins, called caspase-1 or 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.[1]

Clinical significance

An IL-1 blocker, anakinra (Kineret), has been approved for treatment of rheumatoid arthritis. Another, rilonacept, has been approved for Cryopyrin-Associated Periodic Syndromes (CAPS).

Receptor

See also Interleukin-1 receptor.

The receptors for interleukin 1 are:

References

  1. ^ a b Dinarello CA (1994). "The interleukin-1 family: 10 years of discovery". Faseb J. 8 (15): 1314–25. PMID 8001745. http://www.fasebj.org/cgi/content/abstract/8/15/1314.  
  2. ^ Huising MO, Stet RJ, Savelkoul HF, Verburg-van Kemenade BM (2004). "The molecular evolution of the interleukin-1 family of cytokines; IL-18 in teleost fish". Dev. Comp. Immunol. 28 (5): 395–413. doi:10.1016/j.dci.2003.09.005. PMID 15062640.  
  3. ^ 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 (2001). "A new nomenclature for IL-1-family genes". Trends Immunol. 22 (10): 536–7. doi:10.1016/S1471-4906(01)02040-3. PMID 11574262.  
  4. ^ Dunn E, Sims JE, Nicklin MJ, O'Neill LA (2001). "Annotating genes with potential roles in the immune system: six new members of the IL-1 family". Trends Immunol. 22 (10): 533–6. doi:10.1016/S1471-4906(01)02034-8. PMID 11574261.  
  5. ^ HGNC Home Page
  6. ^ Morgan MM, Clayton CC, Heinricher MM (2004). "Dissociation of hyperalgesia from fever following intracerebroventricular administration of interleukin-1beta in the rat". Brain Res. 1022 (1-2): 96–100. doi:10.1016/j.brainres.2004.06.063. PMID 15353218.  
  7. ^ Chantel O Barland, Elizabeth Zettersten, Barbara S Brown, Jianqin Ye, Peter M Elias and Ruby Ghadially: Imiquimod-induced interleukin-1α stimulation improves barrier homeostasis in aged murine epidermis . In: Journal of Investigative Dermatology . 122, No. 2, 15 January 2010, p. 330–336 (PMID 15009713).

Further reading

  • Verweij CL, Bayley JP, Bakker A, Kaijzel EL (2002). "Allele specific regulation of cytokine genes: monoallelic expression of the IL-1A gene". Adv. Exp. Med. Biol. 495: 129–39. PMID 11774556.  
  • 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.  
  • Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines". Mini reviews in medicinal chemistry 5 (12): 1093–101. doi:10.2174/138955705774933383. PMID 16375755.  
  • Schmidt DR, Kao WJ (2007). "The interrelated role of fibronectin and interleukin-1 in biomaterial-modulated macrophage function". Biomaterials 28 (3): 371–82. doi:10.1016/j.biomaterials.2006.08.041. PMID 16978691.  
  • Huynh-Ba G, Lang NP, Tonetti MS, Salvi GE (2007). "The association of the composite IL-1 genotype with periodontitis progression and/or treatment outcomes: a systematic review". J. Clin. Periodontol. 34 (4): 305–17. doi:10.1111/j.1600-051X.2007.01055.x. PMID 17378887.  

External links


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