Interleukin-8

Interleukin-8 is a chemokine produced mainly by stimulated monocytes, but also by macrophages, endothelial cells, hepatocytes, keratinocytes, melanocytes, fibroblasts and various tumor cell lines. Interleukin-8 is encoded by a gene (interleukin-8 gene/alias CXCL8 gene = C-X-C Motif Chemokine Ligand 8), which in humans is located on chromosome 4, where it forms a gene cluster with other cytokine genes.

Its synthesis can be stimulated in many cell types by interleukin-1, interleukin-2, interleukin-3, GMC-SF (granulocyte-monocyte colony-stimulating factor), and TNFalpha. In addition, the formation of interleukin-8 is induced by viruses, bacterial lipopolysaccharides, phytohemagglutinins, and others.

Glucocorticoids such as dexamethasone and betamethasone inhibit production; so do interferon gamma, interleukin-4, and 5'-lipoxygenase inhibitors.

Interleukin-8 is chemotactic for neutrophils and T lymphocytes. IL-8 initiates epidermal proliferation.

Interleukin-8 serves as a mediator in a number of acute and chronic diseases. By activating neutrophil granulocytes, the cytokine is involved in inflammatory responses, especially in the initiation and maintenance of rheumatic diseases. Furthermore, it promotes angiogenesis via activation of vascular endothelial growth factor(VEGF) and matrix metalloproteinase-2, and thus also plays an important role in tumor growth and wound healing. Interleukin-8 is overexpressed in gastric mucosa infected by Helicobacter pylori. In psoriatic lesions, interleukin-8 is overexpressed.

Meta-analyses have confirmed that UVB irradiation in psoriasis lowers serum levels of VEGF and interleukin-8....

A "-251T/A polymorphism" in the promoter region of the interleukin-8 gene increases the risk of developing various carcinomas. A "-251T/A polymorphism" in the promoter region of the interleukin-8 gene increases the risk of various carcinomas, such as breast carcinoma, gastric carcinoma and nasopharyngeal carcinoma.

In detail, interleukin-8 specifically activates neutrophil granulocytes in which chemotaxis and adhesion readiness (expression of adhesion molecules) are increased. Furthermore, an activation of the so-called "oxidative burst" occurs. In basophilic granulocytes and mast cells Il-8 triggers the release of histamine and leukotriene. The cytokine has a chemotactic and activating effect on T-lymphocytes, but inhibits the production of immunoglobulin E (IgE).

Interleukin-8 is a ligand for 2 membrane-bound receptors(CD128 also known as CXCR1andCXR2). These are encoded by different genes which are both localized on chromosome 2 (gene locus q33-q36).

These two receptor types for interleukin-8 are expressed by numerous cell types, but are largely identical in structure and functionality. Both also act as receptors for other cytokines such as the "macrophage inflammatory protein 2 (MIP-2; MIP)", the "melanoma growth stimulatory activity (MGSA)" or the "neutrophil activating protein-2 (NAP-2)". The signal transduction takes place independently of the stimulating ligand via a G protein and leads to an activation of adenyl cyclases, MAP kinases and to an intracellular increase in the Ca2+ concentration.

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