Interleukin 8

Interleukin-8 (IL-8) is a chemokine 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 [Wolff B, Burns AR, Middleton J, Rot A. Endothelial cell "memory" of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies. J Exp Med. 1998 Nov 2;188(9):1757-62. PMID 9802987] [Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G. Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of microvascular endothelial cells. J Exp Med. 1998 Nov 2;188(9):1751-6. PMID 9802986] .

There are more receptors of the surface membrane capable to bind IL-8. The most frequently studied types are the G protein coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity to IL-8 is different in the two receptors (CXCR1>CXCR2).
Toll-like receptors 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.

PBB_Summary
section_title =
summary_text = 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 of Leu25 can block activity of the dimers.
Gene of IL-8 is believed to play a role in the pathogenesis of bronchiolitis, 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. [cite web | title = Entrez Gene: IL8 interleukin 8| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3576| accessdate = ] It is also secreted in urinary tract infections.

Target cells

While neutrophil granulocytes are the primary target cells of IL-8 there is a relative wide range of cells (endothelial cells, macrophages, mast cells, keratinocytes) responding to this chemokine, too. The chemoattractant activity of IL-8 in similar concentrations to vertebrates was proved in Tetrahymena pyriformis, which refers to a phylogenetically well conserved structure and function in the case of this chemokine. [cite journal | author=Köhidai L, Csaba G | title=Chemotaxis and chemotactic selection induced with cytokines (IL-8, RANTES and TNF-alpha) in the unicellular Tetrahymena pyriformis | journal=Cytokine | year=1998 | volume=10 | pages=481–6 | doi=10.1006/cyto.1997.0328 | unused_data=|PMID: 9702410 ]

Function

Primary function of IL-8 is the induction of chemotaxis 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 release), respiratory burst. IL-8 can be secreted by any cells with toll-like receptors 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, 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, and therefore is also known as Neutrophil Chemotactic Factor.

Clinical significance

If a pregnant mother has high levels of interleukin-8, she has a higher risk of inducing schizophrenia in her offspring. [Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, Perrin M, Gorman JM, Susser ES. Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. Am J Psychiatry. 2004 May;161(5):889-95. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15121655 Abstract] [http://ajp.psychiatryonline.org/cgi/content/full/161/5/889#SEC3 fulltext] ] High levels of Interleukin 8 have been shown to reduce the chance of good treatment responses to antipsychotic medication in schizophrenia. [Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC. Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia. J Clin Psychiatry. 2004 Jul;65(7):940-7.]

Interleukin-8 is often associated with inflammation. As an example, it has been cited as a proinflammatory mediator in psoriasis. [http://www.ucsf.edu/dpsl/psoriasis.html]

Nomenclature

IL-8 was renamed CXCL8 by the Chemokine Nomenclature Subcommittee of the Nomenclature Committee of the International Union of Immunological Societies, although its approved gene symbol remains "IL8".

ee also

* Interleukin 8 receptor, alpha
* Interleukin 8 receptor, beta

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Baggiolini M, Clark-Lewis I |title=Interleukin-8, a chemotactic and inflammatory cytokine |journal=FEBS Lett. |volume=307 |issue= 1 |pages= 97–101 |year= 1992 |pmid= 1639201 |doi=
*cite journal | author=Wahl SM, Greenwell-Wild T, Hale-Donze H, "et al." |title=Permissive factors for HIV-1 infection of macrophages |journal=J. Leukoc. Biol. |volume=68 |issue= 3 |pages= 303–10 |year= 2000 |pmid= 10985244 |doi=
*cite journal | author=Starckx S, Van den Steen PE, Wuyts A, "et al." |title=Neutrophil gelatinase B and chemokines in leukocytosis and stem cell mobilization |journal=Leuk. Lymphoma |volume=43 |issue= 2 |pages= 233–41 |year= 2003 |pmid= 11999552 |doi=
*cite journal | author=Smirnova MG, Kiselev SL, Gnuchev NV, "et al." |title=Role of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and interleukin-8 in the pathogenesis of the otitis media with effusion |journal=Eur. Cytokine Netw. |volume=13 |issue= 2 |pages= 161–72 |year= 2003 |pmid= 12101072 |doi=
*cite journal | author=Struyf S, Proost P, Van Damme J |title=Regulation of the immune response by the interaction of chemokines and proteases |journal=Adv. Immunol. |volume=81 |issue= |pages= 1–44 |year= 2004 |pmid= 14711052 |doi=
*cite journal | author=Chakravorty M, Ghosh A, Choudhury A, "et al." |title=Ethnic differences in allele distribution for the IL8 and IL1B genes in populations from eastern India |journal=Hum. Biol. |volume=76 |issue= 1 |pages= 153–9 |year= 2004 |pmid= 15222686 |doi=
*cite journal | author=Yuan A, Chen JJ, Yao PL, Yang PC |title=The role of interleukin-8 in cancer cells and microenvironment interaction |journal=Front. Biosci. |volume=10 |issue= |pages= 853–65 |year= 2006 |pmid= 15569594 |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=

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