Definição e significado de Interleukin_8

Interleukin 8
PDB rendering based on 1IL8.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1ICW, 1IKL, 1IKM, 1IL8, 1ILP, 1ILQ, 1QE6, 1ROD, 2IL8, 3IL8
Identifiers
Symbols	IL8; CXCL8; GCP-1; GCP1; LECT; LUCT; LYNAP; MDNCF; MONAP; NAF; NAP-1; NAP1
External IDs	OMIM: 146930 HomoloGene: 47937 ChEMBL: 2157 GeneCards: IL8 Gene
Gene Ontology Molecular function • interleukin-8 receptor binding • protein binding • chemokine activity Cellular component • extracellular region • extracellular space • intracellular Biological process • angiogenesis • response to molecule of bacterial origin • cellular component movement • inflammatory response • immune response • activation of signaling protein activity involved in unfolded protein response • cell cycle arrest • signal transduction • G-protein coupled receptor signaling pathway • negative regulation of cell proliferation • calcium-mediated signaling • regulation of cell adhesion • neutrophil chemotaxis • endoplasmic reticulum unfolded protein response • receptor internalization • intracellular signal transduction • neutrophil activation • cellular response to fibroblast growth factor stimulus • regulation of retroviral genome replication • negative regulation of G-protein coupled receptor protein signaling pathway • embryonic digestive tract development • induction of positive chemotaxis • cellular response to lipopolysaccharide • cellular response to interleukin-1 • cellular response to tumor necrosis factor • positive regulation of neutrophil chemotaxis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3576	n/a
Ensembl	ENSG00000169429	n/a
UniProt	P10145	n/a
RefSeq (mRNA)	NM_000584.3	n/a
RefSeq (protein)	NP_000575.1	n/a
Location (UCSC)	Chr 4: 74.61 – 74.61 Mb	n/a
PubMed search	[1]	n/a
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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.^[1][2] In humans, the interleukin-8 protein is encoded by the IL8 gene.^[3]

There are many 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.

  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 of Leu25 can block activity of the dimers. 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.^[3][4]

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

When first encountering an antigen, the primary cells to encounter it are the macrophages, which 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 of these chemokines. It serves as a chemical signal that attracts neutrophils at the site of inflammation, 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, macrophages, mast cells, and keratinocytes) responding to this chemokine, too. The chemoattractant activity of IL-8 in similar concentrations to vertebrates was proven in Tetrahymena pyriformis, which refers to a phylogenetically well-conserved structure and function in the case of this chemokine.^[5]

  Clinical significance

Interleukin-8 is often associated with inflammation. As an example, it has been cited as a proinflammatory mediator in gingivitis^[6] and psoriasis.[2]. The fact that Interleukin-8 secretion is increased by oxidant stress, which thereby causes the recruitment of inflammatory cells induces a further increase in oxidant stress mediators, making it a key parameter in localized inflammation.^[7]

If a pregnant mother has high levels of interleukin-8, there is an increased risk of schizophrenia in her offspring.^[8] High levels of Interleukin 8 have been shown to reduce the likelihood of positive responses to antipsychotic medication in schizophrenia.^[9]

  Nomenclature

IL-8 was renamed CXCL8 by the Chemokine Nomenclature Subcommittee of the International Union of Immunological Societies,^[10] although its approved HUGO gene symbol remains IL8.

  See also

• Interleukin 8 receptor, alpha
• Interleukin 8 receptor, beta

  References

  Further reading

PDB gallery 1icw: INTERLEUKIN-8, MUTANT WITH GLU 38 REPLACED BY CYS AND CYS 50 REPLACED BY ALA   1ikl: NMR study of monomeric human interleukin-8 (minimized average structure)   1ikm: NMR study of monomeric human interleukin-8 (30 structures)   1il8: THREE-DIMENSIONAL STRUCTURE OF INTERLEUKIN 8 IN SOLUTION   1ilp: CXCR-1 N-TERMINAL PEPTIDE BOUND TO INTERLEUKIN-8   1ilq: CXCR-1 N-TERMINAL PEPTIDE BOUND TO INTERLEUKIN-8 (MINIMIZED MEAN)   1qe6: INTERLEUKIN-8 WITH AN ADDED DISULFIDE BETWEEN RESIDUES 5 AND 33 (L5C/H33C)   2il8: THREE-DIMENSIONAL STRUCTURE OF INTERLEUKIN 8 IN SOLUTION   3il8: CRYSTAL STRUCTURE OF INTERLEUKIN 8: SYMBIOSIS OF NMR AND CRYSTALLOGRAPHY