Background/Introduction: Interleukin-8 (IL-8), also known as IL-8, GCP-1, and NAP-1, is a heparin-binding 8-9 kDa member of the alpha, or CXC family of chemokines. There are at least 15 human CXC family members that all adopt a three beta-sheet/one alpha-helix structure. Most CXC chemokines show an N-terminal Glu-Leu-Arg (ELR) tripeptide motif (1, 2). IL-8 circulates as a monomer, homodimer, and heterodimer with CXCL4/PF4. The monomer is considered the most bio-active, while the heterodimer can potentiate PF4 activity (3-6). IL-8 oligomerization is modulated by its interactions with matrix and cell surface glycosaminoglycans (GAGs) (7, 8). Mature human IL-8 shares 65-69% amino acid (aa) identity with canine, feline, and porcine IL-8 (9, 10). There is no IL-8 gene counterpart in rodent. Multiple isoforms of IL-8 are generated through both alternative splicing and differential proteolytic cleavage. In humans, alternative splicing generates an iso-form with an eleven aa substitution at the C-terminus (11). Proteolytic processing results in N-terminal truncation of IL-8 and is likely a cell-specific event. For example, fibroblasts and endothelial cells generate the 1-77 form by cleaving IL-8 following Glu21, while monocytes and lymphocytes generate the 6-77 form by cleaving following Leu25. These truncated forms generally show increased bioactivity, particularly through the CXCR1 receptor (12-14). IL-8 can also undergo citrullination on Arg27 of the precursor, a modification that increases its half-life and ability to induce leukocytosis (15, 16). A wide variety of cells secrete IL-8 including monocytes and neutrophils (17), fibroblasts and keratinocytes (18), mast cells (19), visceral smooth muscle cells (20), dendritic cells (21), type II great alveolar cells (22), and endothelial cells (23). IL-8 bioactivity is mediated through two G-protein-coupled receptors, termed CXCR1/IL-8 RA and CXCR2/IL-8 RB (24). CXCR1 is 45-50 kDa in size and is used almost exclusively by IL-8. CXCR2 is 35-40 kDa in size and is used by nearly all CXC chemokines (25, 26). Both CXCR1 and CXCR2 constitutively associate into functional homodimers. They can also heterodimerize, but these complexes dissociate following IL-8 binding (27). CXCR2 responds to low concentrations of IL-8 and is principally associated with chemotaxis and MMP-9 release. CXCR1, in contrast, responds to high concentrations of IL-8 and is associated with respiratory burst and phospholipase D2 activation (26). Thus, CXCR2 ligation induces leukocyte adhesion to activated vascular endothelium and migration to sites of inflammation, while CXCR1 ligation primes neutrophil antimicrobial activity (28). IL-8 can also form a complex with Serpin A1/alpha-1 Antitrypsin, and this prevents IL-8 interaction with CXCR1 (29). In addition to its pro-inflammatory effects, IL-8 is involved in angiogenesis and the pathogenesis of atherosclerosis and cancer (30-33). It induces VEGF expression in vascular endothelial cells and functions as an autocrine factor for EC growth and angiogenesis (34, 35). It is upregulated in atherosclerotic lesions and is elevated in the serum and cerebrospinal fluid following myocardial infarction (36, 37). In cancer, IL-8 promotes epithelial-mesenchymal transition as well as tumor cell invasiveness and metastasis (32, 38-40).
NCBI and Uniprot Product Information
NCBI Description
The protein encoded by this gene is a member of the CXC chemokine family and is a major mediator of the inflammatory response. The encoded protein is secreted primarily by neutrophils, where it serves as a chemotactic factor by guiding the neutrophils to the site of infection. This chemokine is also a potent angiogenic factor. This gene is believed to play a role in the pathogenesis of bronchiolitis, a common respiratory tract disease caused by viral infection. This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q. [provided by RefSeq, Aug 2017]
Uniprot Description
IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively.
Research Articles on IL-8
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Product Notes
The Human IL-8 cxcl8 (Catalog #AAA9135731) is an ELISA Kit and is intended for research purposes only. The product is available for immediate purchase. The AAA9135731 ELISA Kit recognizes Human IL-8. It is sometimes possible for the material contained within the vial of "IL-8/CXCL8, ELISA Kit" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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