Interleukin-8
(IL-8)

Monocyte-derived neutrophil chemotactic factor (MDNCF)
Neutrophil-activating peptide 1 (NAP1)
Granulocyte chemotactic protein 1 (GCP1)
See also: IL-8 at COPE

Gene: maps to 4q12-q21; it has a length of 5.2 kb and contains 4 exons and 3 introns; regulatory sequences including sites for NF-KappaB and AP-1; IL-8 expression pattern very close to that of interleukin-6.
mRNA: size: ~1.6 kb (open reading frame: 297 bases); induced by interleukin-1, tumor necrosis factor, phorbol esters, and agents increasing intracellular cyclic AMP; reduced by glucocorticoids, interleukin-4, transforming growth factor-ß.
Protein: a 72-amino acids (aa), 8.4-kDa, non-glycosylated protein. It is produced by processing of a 99-aa precursor protein. Variants of IL-8 containing 79, 77 or 69 aa have been isolated from conditioned medium of lipopolysaccharide-stimulated lymphocytes. IL-8 is secreted by several types of cells in response to inflammatory stimuli.

Cell lines:
- The in vitro effect of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated on activation, normal T-cells, expressed and secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), IL-8, interferon inducible protein-10 (IP-10), neutrophil-activating peptide-2 (NAP-2), growth-related protein (GRO)-alpha and GRO-gamma, on the migration of 3 human breast carcinoma cell (BCC) lines, MCF-7, T47D and ZR-75-1, was investigated using a microchemotaxis chamber to assess migration across fibronectin-coated polycarbonate membranes. MCF-7 cells responded chemotactically to all chemokines tested in a pattern which was dose and time dependent, although responses to the different chemokines were variable. ZR-75-1 responded to MIP-1beta and GRO-alpha, giving maximum migration indices of 3.7 and 5.3, respectively, and exhibited a migratory response to MIP-1alpha, IL-8 and MCP-1 although to a lower degree. T47D was unresponsive to the chemokines tested, but both MCF-7 and T47D cells bound radiolabelled ligands with binding constants (Kd) ranging from 0.6 to 2.2 nM and 0.6 to 2.1 nM, respectively. The specificity of the chemotactic response of MCF-7 to MIP-1alpha and MIP-1beta was confirmed using chemokine-specific neutralising antibodies and heat denaturation, and was demonstrated to involve G protein and cyclic AMP signalling pathways. MIP-1beta and MIP-1alpha were shown to induce changes in the organisation of the actin cytoskeleton and the level of F-actin in MCF-7 cells, as determined using flow cytometric analysis and confocal microscopy (Youngs S.J. et al., 1997).

Tumors:
- The presence of mRNA transcripts for IL-8 in normal and neoplastic human breast tissue was investigated. There was a significant difference in expression of IL-8 transcripts, which was higher in the neoplastic population (Green A.R. et al., 1997).

- IL-8 supports angiogenesis and could play a role in angiogenesis-dependent tumor growth.

Green A.R. et al. (1997) Expression of cytokine messenger RNA in normal and neoplastic human breast tissue: identification of interleukin-8 as a potential regulatory factor in breast tumours. Int. J. Cancer 72, 937-941.
Mahé Y. et al. (1991) Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements. J. Biol. Chem. 266, 13759-13763.
Matsushima K. et al. (1988) Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J. Exp. Med. 167, 1883-1893.
Modi W.S. et al. (1989) Chromosome mapping and RFLP analyses of monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8). (Abstract) Cytogenet. Cell Genet. 51, 1046.
Modi W.S. et al. (1990) Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily. Hum. Genet. 84, 185-187.
Mukaida N. et al. (1989) Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J. Immunol. 143, 1366-1371.
Youngs S.J. et al. (1997) Chemokines induce migrational responses in human breast carcinoma cell lines. Int. J. Cancer 71, 257-266.