Drug Target and Biomarker: CXCL8 (G3576)

NCBI ID: G3576

CXCL8

Drug Target and Biomarker: CXCL8

IL-8, also referred to as CXCL8, plays a significant role in various cellular pathways and biological functions. It is involved in the activation and release of IL-8 itself, as well as other proteins such as ILK and RhoA. In specific conditions like mesenchymal glioblastoma (GBM), IL-8 secretion by MES GSCs affects the survival and proliferation of endothelial cells, leading to vessel expansion. Furthermore, IL-8 is associated with glucotoxicity and the mesothelial to mesenchymal transition in peritoneal mesothelial cells, which can be prevented by GCN-2 kinase activation.

Regarding the signaling pathways of CXCL8, it binds G protein-coupled receptors (CXCR1 or CXCR2), activating G protein and subsequently stimulating PLC and PI3K pathways. These pathways induce the phosphorylation of PKC and Akt, respectively, which are associated with the survival, angiogenesis, and migration of tumor cells. Additionally, CXCL8 activates non-receptor tyrosine kinases and members of the RhoGTPase family, promoting cell proliferation, survival, motility, and invasion. The Raf-1/MAP/Erk signaling cascade also contributes to cell proliferation and survival.

In summary, IL-8 (CXCL8) has diverse roles in cellular pathways and functions, including vessel expansion, glucotoxicity, and regulation of tumor cells through various signaling pathways .

In the context of infection with highly pathogenic avian influenza virus (HPAIV) subtypes H5N1, H7N7, and H7N9, IL-8 expression is potentiated along with IFN-beta and IL-6. This heightened expression of IL-8, IFN-beta, and IL-6 is associated with tissue damage and high mortality during HPAIV infections.

Cycling hypoxia in cancer leads to the activation of HIF-1 and NF-kappaB, resulting in increased production of IL-8 along with other factors like VEGF-A, CCL2/MCP-1, CXCL1/GRO-alpha, and PGE2. IL-8 directly contributes to angiogenesis, and its production leads to the recruitment of tumor-associated macrophages (TAM) and tumor-associated neutrophils (TAN) to the tumor niche.

TNF-induced inflammation triggers the production of IL-8 through NFkappaB signaling, and its secretion is associated with the regulation of metabolism, mitochondria ultrastructure, and network. Prolonged treatment with TNF causes an overflow of antioxidant defenses, leading to dysfunction of mitochondrial membrane complexes and activation of the apoptotic cascade.

In the treatment of osteoarthritis (OA), biofield modulation therapy (BMO) interacts with IL-6, MAPK1, TNF, IL-1, CXCL8, and VEGFA. These interactions occur in pathways like TNF pathway, NF-kappaB pathway, and HIF-1 pathway.

In the context of chronic obstructive pulmonary disease (COPD), IL-8 (CXCL8) plays a significant role. At the stable state, CXCL8 attracts neutrophils and monocytes into bronchial tissue, whereas during exacerbations, its production is enhanced, leading to increased recruitment of monocytes and T cells in the bronchial tissue. This immune response is often triggered by microbial infection.

Protein Name: C-X-C Motif Chemokine Ligand 8

Functions: Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:7636208, PubMed:18692776). Also plays an important role in neutrophil activation (PubMed:9623510, PubMed:2145175). Released in response to an inflammatory stimulus, exerts its effect by binding to the G-protein-coupled receptors CXCR1 and CXCR2, primarily found in neutrophils, monocytes and endothelial cells (PubMed:1840701, PubMed:1891716). G-protein heterotrimer (alpha, beta, gamma subunits) constitutively binds to CXCR1/CXCR2 receptor and activation by IL8 leads to beta and gamma subunits release from Galpha (GNAI2 in neutrophils) and activation of several downstream signaling pathways including PI3K and MAPK pathways (PubMed:8662698, PubMed:11971003)

The "CXCL8 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about CXCL8 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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