IL-8/CXCL8

IL-8 (CXCL8) belongs to the ELR⁺ CXC chemokines family. IL-8 is initially produced as a protein of 99 amino acids that undergoes cleavage to form active IL-8 isoforms, a 77 amino acid peptide in non-immune cells or a 72 amino acid peptide in monocytes and macrophages. The gene encoding IL-8 is located on chromosome 4q13-q21. Dimerisation of IL-8 forms the structural basis for receptor binding. IL-8 is expressed by various cells including monocytes, macrophages, leukocytes, endothelial cells, and epithelial cells^[1][2][3].
IL-8 is responsible for the recruitment and activation of neutrophils and granulocytes to the site of inflammation. IL-8 is almost undetectable in physiological states, but is rapidly induced by pro-inflammatory cytokines such as TNFα and IL-1β. The function of IL-8 mainly relies on its interaction with specific cell surface GPCR, CXCR1 and CXCR2. In addition, IL-8 is reported to promote integrin β3 upregulation and the invasion of hepatocellular carcinoma cells through activation of the PI3K/Akt pathway. In odontogenic lesions, IL-8 has been proven to be highly expressed in ameloblastoma epithelial cells and irreversible pulpitis. In rheumatoid arthritis and other inflammatory joint diseases IL-8 could bring about the accumulation of neutrophils, which are considered a major source of cartilage-degrading enzymes. IL-8 stimulates the MAPK and tyrosine phosphorylation of cellular proteins. Tumour cells and fibroblasts communicate with each other, including autocrine and paracrine factors, including IL-8, resulting in the upregulation of MMP2 and MMP9 degradable extracellular matrix (ECM) components that trigger tumour invasion^[1][2][3][4].