Interleukin 8
Encyclopedia
Interleukin-8 is a chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...

 produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies. In humans, the interleukin-8 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...

 is encoded by the IL8 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...

.

There are more receptors of the surface membrane capable to bind IL-8; the most frequently studied types are the G protein coupled
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

 serpentine receptors CXCR1
Interleukin 8 receptor, alpha
Interleukin 8 receptor, alpha is a chemokine receptor. IL8RA is its human gene. IL8RA has also been designated CD181 , and CXCR1. CXCR1 is now the IUPHAR Committee on Receptor Nomenclature and Drug Classification recommended name.-Clinical significance:Blocking CXCR1 Interleukin 8 receptor, alpha ...

 and CXCR2
Interleukin 8 receptor, beta
Interleukin 8 receptor, beta is a chemokine receptor. IL8RB is also known as CXCR2, and CXCR2 is now the IUPHAR Committee on Receptor Nomenclature and Drug classification-recommended name.-Function:...

. Expression and affinity to IL-8 is different in the two receptors (CXCR1 > CXCR2). Toll-like receptor
Toll-like receptor
Toll-like receptors are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors that recognize structurally conserved molecules derived from microbes...

s are the receptors of the innate immune system. These receptors recognize antigen patterns (like LPS in gram negative bacteria). Through a chain of biochemical reactions IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response.

Function

The protein encoded by this gene is a member of the CXC chemokine family. This chemokine is one of the major mediators of the inflammatory response. This chemokine is secreted by several cell types. It functions as a chemoattractant, and is also a potent angiogenic factor. Both monomer and homodimer forms of IL-8 were reported as potent inducers of CXCR1 and CXCR2, the homodimer proved to be more potent, however, methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...

 of Leu25 can block activity of the dimers. IL-8 is believed to play a role in the pathogenesis of bronchiolitis
Bronchiolitis
Bronchiolitis is inflammation of the bronchioles, the smallest air passages of the lungs. It usually occurs in children less than two years of age and presents with coughing, wheezing, and shortness of breath. This inflammation is usually caused by viruses...

, a common respiratory tract disease caused by viral infection. This gene and other ten members of the CXC chemokine gene family form a chemokine gene cluster in a region mapped to chromosome 4q.

Primary function of IL-8 is the induction of chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...

 in its target cells (e.g. neutrophil granulocytes). In neutrophils series of cell-physiological responses required for migration and its target function phagocytosis are also induced like increase of intracellular Ca2+, exocytosis (e.g. histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...

 release), respiratory burst
Respiratory burst
Respiratory burst is the rapid release of reactive oxygen species from different types of cells....

.
IL-8 can be secreted by any cells with toll-like receptor
Toll-like receptor
Toll-like receptors are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors that recognize structurally conserved molecules derived from microbes...

s which are involved in the innate immune response. IL-8's primary function is to recruit neutrophils to phagocytose the antigen which trigger the antigen pattern toll-like receptors.

When first encountering an antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

, the primary cells to encounter it are the macrophages who phagocytose the particle. Upon processing, they release chemokines to signal other immune cells to come in to the site of inflammation. IL-8 is one such chemokine. It serves as a chemical signal that attracts neutrophils at the site of inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

, and therefore is also known as neutrophil chemotactic factor.

Target cells

While neutrophil granulocytes are the primary target cells of IL-8 there is a relative wide range of cells (endothelial cells, macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s, mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...

s, keratinocyte
Keratinocyte
Keratinocytes are the predominant cell type in the epidermis, the outermost layer of the human skin, constituting 95% of the cells found there. Those keratinocytes found in the basal layer of the skin are sometimes referred to as "basal cells" or "basal keratinocytes"...

s) responding to this chemokine, too. The chemoattractant activity of IL-8 in similar concentrations to vertebrates was proved in Tetrahymena
Tetrahymena
Tetrahymena are free-living ciliate protozoa that can also switch from commensalistic to pathogenic modes of survival. They are common in fresh-water. Tetrahymena species used as model organisms in biomedical research are T. thermophila and T. pyriformis.- T...

 pyriformis, which refers to a phylogenetically well conserved structure and function in the case of this chemokine.

Clinical significance

Interleukin-8 is often associated with inflammation. As an example, it has been cited as a proinflammatory mediator in gingivitis
Gingivitis
Gingivitis is a term used to describe non-destructive periodontal disease. The most common form of gingivitis is in response to bacterial biofilms adherent to tooth surfaces, termed plaque-induced gingivitis, and is the most common form of periodontal disease...

 and psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

.http://www.ucsf.edu/dpsl/psoriasis.html. The fact that Interleukin-8 secretion is increased by oxidant stress and conversely, Interleukin-8, by causing recruitment of inflammatory cells induces a further increase in oxidant stress mediators, makes it a key parameter in localized inflammation.

If a pregnant mother has high levels of interleukin-8, there is an increased risk of schizophrenia
Schizophrenia
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 her offspring. High levels of Interleukin 8 have been shown to reduce the likelihood of positive responses to antipsychotic medication in schizophrenia.

Nomenclature

IL-8 was renamed CXCL8 by the Chemokine Nomenclature Subcommittee of the International Union of Immunological Societies
International Union of Immunological Societies
The International Union of Immunological Societies, a member of the International Council for Science, is an organization which serves as an umbrella organization for many national immunological societies. The organization was founded in 1969....

, although its approved HUGO
Human Genome Organisation
The Human Genome Organisation is an organization involved in the Human Genome Project, a project about mapping the human genome. HUGO was established in 1989 as an international organization, primarily to foster collaboration between genome scientists around the world...

gene symbol remains IL8.

Further reading

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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