Interleukin-8
- OMIM: 146 930
- UniProt: P10145
- MGI: -
Interleukin -8 (short: IL-8) or CXCL8 ( for CXC motif chemokine 8) is an endogenous neurotransmitter from the group of CXC motif chemokines. CXCL8 in particular produced by endothelial cells, monocytes, epithelial cells and fibroblasts. As a mediator of inflammation this cytokine in the chemotactic recruitment of leukocytes, in particular neutrophils into the inflamed tissue is involved. Moreover, CXCL8 an angiogenesis factor and participates as such in the formation and development of new blood vessels.
It was discovered in 1987 by Marco Baggiolini and others at the University of Bern.
- 2.1 immune system
- 2.2 angiogenesis
Biochemistry
Genetics
The CXCL8 human gene on chromosome 4 in the CXC chemokine cluster region gene locus in the q13 -21 encodes a 99 amino acids consisting of Präcursorprotein. Also there is a regulatory sequence with binding sites for the transcription factors AP-1, NF-KB, C / EBP, which is used to control gene expression. The protein of CXCL8 is thus induced by activators of transcription factors, such as interleukin 1, interleukin 3, interleukin 6, tumor necrosis factor - α, interferon - γ, GM-CSF, lipopolysaccharides, reactive oxygen species and other cellular stress factors, while the anti -inflammatory cytokines interleukin 4 and interleukin-10 inhibit its biosynthesis.
Protein structure
From the Präcursorprotein consisting of 99 amino acids consisting of a 79 amino acid form of CXCL8 is released after cleavage of a signal sequence. This peptide is subject to its N-terminal extracellular further modifications so that different functional isoforms are formed by 69-79 amino acids. The dominant, produced by the immune cell variant consists of 72 amino acids, while consisting of 77 amino acids variant is mainly produced by non - immune cells.
Like almost all chemokines CXCL8 is a basic peptide. It contains four conserved cysteines that are connected by two disulfide bridges. CXCL8 is in significant quantities as a dimer, wherein the monomeric form of the protein for its biological effect is sufficient.
Signal transduction
CXCL8 mediated its effects via binding and activation of G- protein-coupled receptors CXCR1 and CXCR2. Via activation of G- proteins, these receptors trigger a signal transduction cascade, which include activation of adenylyl cyclases, MAP kinases and an intracellular increase in Ca2 concentration. Moreover, CXCL8 binds to the structurally related DARC. However, its function is largely unknown.
Function
Immune system
An important point of the chemokine are neutrophils. The main biological effects of IL-8 on granulocytes include the promotion of chemotaxis, the stimulation of the expression of adhesion molecules and activation with release of oxygen radicals, and granules, which are mediated by the chemokine receptors CXCR1 and CXCR2. This ensures that especially neutrophils arrive at the site of infection on the basis of the IL -8 gradient.
Angiogenesis
The pro- angiogenic effects of CXCL8 is due to the effect on endothelial cells. As a chemotactic cytokine CXCL8 promotes migration of endothelial cells into the extracellular matrix of the tissue. At the same time CXCL8 has an anti - apoptotic on endothelial cells and promotes their proliferation to form capillary structures. This mechanism is maintained by the CXCL8 - induced release of extracellular matrix metalloproteases decomposing. This effect plays a significant role during the menstruation, and wound healing. Also for the supply and thus the growth of tumors is the pro- angiogenic effect of critical importance.