Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transformation of chicken embryo fibroblasts (CEF) by the Rous sarcoma virus leads to the constitutive expression of the cellular gene designated CEF-4. With specific antisera, we confirmed that transformed cells actively synthesize and secrete a 6 kDa polypeptide corresponding to the CEF-4 gene product. The expression of CEF-4 was investigated by Northern and immunoprecipitation analyses. Upon activation of pp60v-src in cells infected by a ts mutant of RSV, the expression of CEF-4 was biphasic with an early transient and a late constitutive period of expression. CEF-4 was expressed in cells transformed by a variety of oncogenes, but the level of constitutive expression differed quantitatively among transformed cells. Cells transformed by v-myc alone did not express CEF-4. Unlike other members of the interleukin 8 gene family, CEF-4 was induced in response to a broad spectrum of growth factors and inflammatory agents. Dexamethasone repressed the induction of CEF-4 by lipopolysaccharides but had little or no effect on the response to serum or pp60v-src. These data emphasize the complexity of CEF-4 expression and suggest the existence of multiple levels or pathways of CEF-4 regulation in normal and transformed cells.
 ...
PMID:Complex expression pattern of the CEF-4 cytokine in transformed and mitogenically stimulated cells. 165 64

The chicken gene, 9E3/CEF4, is a small inducible cytokine highly homologous to human IL-8 and gro alpha. It is overexpressed during wound healing and in the tissues around tumours induced by Rous sarcoma virus. More is known about the expression of 9E3 in vivo than any other of the small cytokines, yet little is known about its biochemical characteristics and functions. Here we report on some of the biochemical properties of the 9E3 gene product, the kinetics of protein secretion, the post-secretory processing of the protein, and on its association with ECM molecules. The protein: (1) is synthesized and secreted in < 10 min; (2) is not glycosylated and does not bind heparin with high affinity; (3) is secreted as a 9 kDa form and is processed to a 6-7 kDa form by plasmin, an enzyme released at wound sites and produced in association with tumours; (4) the small form binds to interstitial collagen, laminin and to a lesser extent to proteoglycan, and does not bind to collagen IV or fibronectin. This is the most rapidly secreted protein yet described in eukaryotic cells and is the first of the small inducible cytokines to be found to associate with ECM molecules other than glycosaminoglycans. Our results suggest that, given the appropriate stimulus, the level of the 9E3 cytokine could be elevated very rapidly, resulting in similarly rapid biological responses. The different modes of availability of the two forms of the molecule suggest that the two isoforms may play different roles in vivo.
 ...
PMID:The 9E3/CEF4 cytokine: kinetics of secretion, processing by plasmin, and interaction with extracellular matrix. 881 41

The 9E3/CEF4 gene was one of the first inducible chemokine genes to be discovered. Its product, the chicken chemotactic and angiogenic factor (cCAF), is highly homologous to IL-8. It is expressed at low levels in tissues of mesenchymal origin but is highly expressed shortly after wounding and persists throughout the period of granulation tissue formation. It also is highly expressed around Rous sarcoma virus-induced tumors. The most potent natural stimulator of this gene is thrombin and in vivo cCAF is chemotactic for monocytes and lymphocytes and is angiogenic. The chemotactic properties can be potentially important in the inflammatory response and in the deterrence of tumors, whereas the angiogenic properties could be important in wound repair and tumor growth. The very rapid stimulation of 9E3 by thrombin and fast synthesis and secretion of cCAF suggest that this is a new type of stress response protein whose rapid production is designed to protect tissues rather than individual cells.
 ...
PMID:The 9E3/CEF4 gene and its product the chicken chemotactic and angiogenic factor (cCAF): potential roles in wound healing and tumor development. 946 87