Regulation of Human Interleukin 8 Gene Expression and Binding of Several Other Members of the Intercrine Family to Receptors for Interleukin-8
Recruitment of leukocytes into tissues presumeably involves the local release of leukocyte activating and chemotactic mediators in response to injury-induced inflammatory reactions. We have recently purified major neutrophil, monocyte, and lymphocyte chemotactic factors to homogeneity from the conditioned media of human PBMC or monocytic cell line stimulated with mitogens and have shown that these chemotactic factors are structurally distinct from known cytokines, including IL-1 or TNF (1,2,3). Neutrophil chemotactic factor was structurally identical to T lymphocyte chemotactic factor and has been renamed IL-8 (3). IL-8 is distinct from the monocyte chemotactic and activating factor (MCAF) (2). cDNA cloning of IL-8 has been performed and the cDNA encodes a 99 amino acid precursor form of IL-8 (4). There is a typical signal peptide at the amino terminal end of the IL-8 precursor molecule and the mature processed soluble extracellular form of IL-8 consists of 72 amino acids. IL-8 shows considerable amino acid sequence homology to several human cytokines, such as β-thromboglobulin, platelet factor 4, gamma-IP 10 and GRO/MGSA. For ease of communication we will identify these cytokines as members of the intercrine family in this article. Such a generic term may provide useful in providing a name for members of this cytokine family based on their chromosomal location when they are precisely determined over the next few years. For example, cytokines such as IL-8 that are located on chromosome 4 can therefore be assigned a number in the intercrine α subfamily, whereas MCAF and the others on chromosome 17 can be assigned a number in the intercrine β subfamily.
KeywordsChemotactic Factor Chemotactic Cytokine Human PBMC Neutrophil Chemotactic Factor Octamer Motif
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