CXCL8-gene

The CXCL8 gene (CXCL8 stands for: C-X-C Motif Chemokine Ligand 8), is a protein coding gene located on chromosome 4q13.3. The CXCL8 gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q.

The encoded protein is commonly referred to as interleukin-8 (IL-8). Interleukin-8 is a cytokine that belongs to the CXC chemokine family. It is an important mediator of the inflammatory response. IL-8 is secreted by mononuclear macrophages, neutrophils, eosinophils, T lymphocytes, epithelial cells and fibroblasts. Interleukin-8 acts as a chemotactic factor by directing neutrophils to the site of infection. Bacterial and viral products rapidly induce the expression of IL-8. IL-8 is also involved with other cytokines in the proinflammatory signaling cascade and plays a role in systemic inflammatory response syndrome (SIRS).

Interluekin-8 exerts its effects by binding to the G-protein-coupled receptors CXCR1 and CXCR2, which are mainly found in neutrophils, monocytes, and endothelial cells. The G-protein heterotrimer (alpha, beta, gamma subunits) binds constitutively to the CXCR1/CXCR2 receptor. Activation by IL8 leads to activation of multiple downstream signaling pathways, including PI3K and MAPK pathways.

The Intelrueikin-8 gene is thought to play a role in the development of lower respiratory tract bronchiolitis, a common respiratory disease caused by respiratory syncytial virus (RSV). This proinflammatory protein is also suspected to play a role in coronary artery disease and endothelial dysfunction. Furthermore, it plays a role in the cytokine network activated in psoriasis. Interleukin-8 is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis, and metastasis (Fu X et al. (2023). The chemokine is a potent angiogenic factor.

Binding of IL-8 to one of its receptors (IL-8RB/CXCR2) increases blood vessel permeability. Increasing IL-8 levels are positively correlated with the severity of various disease states (e.g., sepsis).

Diseases associated with CXCL8 include Adult Respiratory Distress Syndrome and versch. Tumors (melanoma, colon carcinoma, and others). Related signaling pathways include MIF-mediated glucocorticoid regulation and the TGF-beta pathway.

1. Fu X et al (2023) CXCL8 and the peritoneal metastasis of ovarian and gastric cancer. Front Immunol 14:1159061.
2. Rasool M et al (2021) Overexpression of CXCL8 gene in Saudi colon cancer patients. Saudi J Biol Sci 28: 6045-6049.
3. Yu X et al. (2022) CXCL8, CXCL9, CXCL10, and CXCL11 as biomarkers of liver injury caused by chronic hepatitis B. Front Microbiol 13:1052917.