Interleukin - 8

Interleukin - 8 (IL - 8), also known as CXCL8, belongs to the family of proinflammatory CXC chemokines. Its production takes place in phagocytes and mesenchymal cells, which have been confronted by a stimulating stimulus. IL - 8 activates chemotaxis, inducing exocytosis and the oxidative burst. IL-8 has an original length of 99 amino acids. After expression, IL-8 is shortened to 77 amino acids (in non-immune cells) or 72 amino acids (in monocytes and macrophages). This posttranslational modification activates IL - 8 and makes it signal competent. The expression of IL - 8 is influenced by many factors. Among the most important factors are the activator protein-1 and the factor- NF-κB mediated transcriptive activity. In addition, gene regulation of IL-8 by signaling agents, e.g. Tumor necrosis factor - α, chemotherapeutic agents and steroid hormones. The mature IL-8 is activated upon binding to two G protein-coupled receptors located on the cell surface. These receptors are referred to as CXCR1 and CXCR2. Signal transduction finally takes place through the conformational change of the receptor. The epitopes on the intracellular loops and at the carboxyl end of the receptor are exposed so that coupling to functional heterodimeric G proteins can take place. IL - 8 plays an important role in the development of cancers due to its many functions. Thus, IL-8 strongly influences the microenvironment of tumors. The excretion of IL - 8 from cancer cells, promotes the proliferation and survival of cancer cells through the activation of autocrine signaling pathways. IL - 8 is also capable of inducing angiogenesis and allowing chemotactic infiltration of neutrophils into the tumor cell. Further investigation of CXC chemokine signaling, eventually IL-8, is needed to sensitize cancer and tumors.

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Referenzen

Baggiolini, M., Walz, A., & Kunkel, S. L. (1989). Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. The Journal of clinical investigation, 84(4), 1045-1049.

Keatings, V. M., Collins, P. D., Scott, D. M., & Barnes, P. J. (1996). Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. American journal of respiratory and critical care medicine, 153(2), 530-534.

Waugh, D. J., & Wilson, C. (2008). The interleukin-8 pathway in cancer. Clinical cancer research, 14(21), 6735-6741.