Interleukin-8 (IL-8) IL-8 is an interleukin that acts as a chemokine for leukocytes and connective tissue cells. IL-8 is produced by monocytes, neutrophils, and NK cells and is acts as a homing defice for neutrophils, basophils and [T lymphocyte|T-cells.]]
One of the first chemokines to be isolated; one of the C-X-C family (8 kD). Secreted by a variety of cells and potently chemokinetic and chemotactic for neutrophils and basophils but not monocytes. Receptor is G-protein coupled.
Members of the chemokine family fall mostly into two broad groups-CC chemokines (or β-chemokines) with two adjacent cysteines near the amino terminus of the protein, and CXC chemokines (or α-chemokines) in which the cysteines are separated by an amino acid. The two groups of chemokines act on different receptors. CC chemokines bind to CC chemokine receptors, of which nine have been discovered to date, designated CCR1-9. CXC chemokines bind to CXC chemokine receptors, of which five have been discovered to date, designated CXCR1-5. These receptors are expressed on the surface of different cell types. CXC chemokines which have a specific amino acid sequence (or motif) of Glutamic acid-Leucine-Arginine (or ELR for short) immediately before the first cysteine induce the migration of neutrophils. An example of this is interleukin-8 (IL-8) which induces neutrophils to leave the bloodstream and enter into the surrounding tissue.
Chronic hyperglycemia is an established risk factor for endothelial damage. It remains unclear, however, whether brief hyperglycemic episodes after acute stress alter the function of vascular endothelial cells in response to endotoxin. Hyperglycemic conditions enhance IL-8 production by vascular endothelial cells, and this response is augmented by LPS. Infections may foster neutrophil accumulation at injury sites. These results suggest that it is important to manage even short-term increases in blood glucose after acute stress.()
Genetic polymorphism of interleukin-8 (IL-8) is associated with Helicobacter pylori-induced duodenal ulcer
Eur Cytokine Netw. 2004 Oct-Dec;15(4):353-8. Gyulai Z, Klausz G, Tiszai A, Lenart Z, Kasa IT, Lonovics J, Mandi Y.
- BACKGROUND AND AIMS: Helicobacter pylori infection almost invariably causes chronic gastritis, but only a proportion of the infected subjects develop peptic ulcers. The local inflammation associated with H. pylori infection is characterized by an increased production of the proinflammatory cytokines IL-1-B, IL-6, IL-8 and TNF-alpha. Since such cytokine production is often determined by the genetic polymorphism of regions regulating cytokine gene expression, we investigated the relationship between TNF-alpha and IL-8 polymorphisms and the development of duodenal ulcer disease. We also sought a correlation between the promoter polymorphism of the lipopolysaccharide (LPS) receptor CD14 and the formation of peptic ulcer, because CD14 plays a crucial role in the initiation of the cytokine cascade. METHODS: Genomic DNA extracted from the peripheral blood of 69 patients with H. pylori-positive duodenal ulcer disease and 47 H. pylori-positive healthy controls was analyzed for TNF-alpha -308 promoter polymorphism by RFLP, and for IL-8 -251 polymorphism by ARMS. Genetic polymorphism within the promoter of the CD14 gene was identified using the LightCycler instrument via melting point analysis. RESULTS: No significant correlation could be revealed between the TNF-alpha and CD14 promoter polymorphisms and the clinical outcome of H. pylori infection. The IL-8 A/T heterozygote mutant variant was detected with a significantly higher frequency (65.22%) among the ulcer patients than among the healthy, H. pylori-positive blood donors (36.17%), while the frequency of the normal allelic genotype (TT) was significantly higher in the control group (44.6% vs 15.9%). CONCLUSION: Analysis of the genetic predisposition to enhanced cytokine production revealed a significant association only for the IL-8 polymorphism. This observation draws attention to the possible importance of IL-8 polymorphism as a genetic predisposing factor in the pathomechanism of H. pylori-induced duodenal ulcer disease, and to the relative protection from duodenal ulcer disease that is associated with the TT genotype.
Effect of herbal melanin on IL-8: A possible role of Toll-like receptor 4 (TLR4)
Biochem Biophys Res Commun. 2006 Apr 28;
El-Obeid A, Hassib A, Ponten F, Westermark B.
- The production of IL-8 can be induced by LPS via TLR4 signaling pathway. In this study, we tested the effect of a herbal melanin (HM) extract, from black cumin seeds (Nigella sativa L.), on IL-8 production. We used HM and LPS in parallel to induce IL-8 production by THP-I, PBMCs, and TLR4-transfected HEK293 cells. Both HM and LPS induced IL-8 mRNA expression and protein production in THP-1 and PBMCs. On applying similar treatment to HEK293 cells that express TLR4, MD2, and CD14, both HM and LPS significantly induced IL-8 protein production. We have also demonstrated that HM and LPS had identical effects in terms of IL-8 stimulation by HEK293 transfected with either TLR4 or MD2-CD14. Melanin extracted from N. sativa L. mimics the action of LPS in the induction of IL-8 by PBMC and the other used cell lines. Our results suggest that HM may share a signaling pathway with LPS that involves TLR4.