Interleukin 8

Interleukin 8 (IL-8) or CXCL8 is a is_associated_with::chemokine produced by is_associated_with::macrophages and other cell types such as is_associated_with::epithelial cells, airway smooth muscle cells and endothelial cells. is_associated_with::Endothelial cells store IL-8 in their storage vesicles, the is_associated_with::Weibel-Palade bodies. In humans, the interleukin-8 is_associated_with::protein is encoded by the IL8 is_associated_with::gene. IL-8 is initially produced as a precursor peptide of 99 amino acids long which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages.

There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2). 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
IL-8, also known as neutrophil chemotactic factor, has two primary functions. It induces is_associated_with::chemotaxis in target cells, primarily neutrophils but also other granulocytes, causing them to migrate toward the site of infection. IL-8 also induces phagocytosis once they have arrived. IL-8 is also known to be a potent promoter of is_associated_with::angiogenesis. In target cells, IL-8 induces a series of physiological responses required for migration and phagocytosis, such as increases in intracellular Ca2+, exocytosis (e.g. is_associated_with::histamine release), and the is_associated_with::respiratory burst.

IL-8 can be secreted by any cells with is_associated_with::toll-like receptors that are involved in the innate immune response. Usually, it is the is_associated_with::macrophages that see an antigen first, and thus are the first cells to release IL-8 to recruit other cells. Both monomer and is_associated_with::homodimer forms of IL-8 have been reported to be potent inducers of the chemokine receptors CXCR1 and CXCR2. The homodimer is more potent, but is_associated_with::methylation of Leu25 can block the activity of homodimers.

IL-8 is believed to play a role in the pathogenesis of is_associated_with::bronchiolitis, a common respiratory tract disease caused by viral infection.{fact}

IL-8 is a member of the CXC chemokine family. The genes encoding this and the other ten members of the CXC chemokine family form a cluster in a region mapped to chromosome 4q.

Target cells
While neutrophil granulocytes are the primary target cells of IL-8, there are a relatively wide range of cells (is_associated_with::endothelial cells, is_associated_with::macrophages, is_associated_with::mast cells, and is_associated_with::keratinocytes) that respond to this chemokine. The chemoattractant activity of IL-8 in similar concentrations to vertebrates was proven in is_associated_with::Tetrahymena pyriformis, which suggests a phylogenetically well-conserved structure and function for this chemokine.

Clinical significance
Interleukin-8 is often associated with inflammation. As an example, it has been cited as a proinflammatory mediator in is_associated_with::gingivitis and is_associated_with::psoriasis.. Interleukin-8 secretion is increased by oxidant stress, which thereby cause the recruitment of inflammatory cells and induces a further increase in oxidant stress mediators, making it a key parameter in localized inflammation. IL-8 was shown to be associated with is_associated_with::obesity.

IL-8 has also been implied to have a role in colorectal cancer by acting as an is_associated_with::autocrine growth factor for colon carcinoma cell lines or the promotion of division and possible migration by cleaving is_associated_with::metalloproteinase molecules.

If a pregnant mother has high levels of interleukin-8, there is an increased risk of is_associated_with::schizophrenia 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 is_associated_with::International Union of Immunological Societies,. Its approved HUGO gene symbol is CXCL8.

Regulation of Expression
The expression of IL-8 is negatively regulated by a number of mechanisms. MiRNA-146a/b-5p indirectly represses IL-8 expression by silencing the expression of IRAK1. Additionally, the 3'UTR of IL-8 contains a A/U-rich element that makes it extremely unstable under certain conditions. IL-8 expression is also regulated by the transcription factor is_associated_with::NF-κB. is_associated_with::NF-κB regulation represents a novel anti-IL-8 therapy for use in inflammatory diseases such as cystic fibrosis.