interleukin-8-mediated signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by interleukin-8 binding to its receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:nhn, GOC:signaling]

Interleukin-8 (IL-8), also known as CXCL8, is a potent chemoattractant and pro-inflammatory cytokine that plays a crucial role in the innate immune response. Its signaling pathway is initiated when IL-8 binds to its cognate receptors, CXCR1 and CXCR2, which are G protein-coupled receptors (GPCRs) expressed on various immune cells, including neutrophils, macrophages, and T cells. Upon ligand binding, the GPCRs undergo a conformational change that triggers the activation of a signaling cascade involving heterotrimeric G proteins. The activation of G proteins leads to the activation of phospholipase C (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3). DAG activates protein kinase C (PKC), while IP3 mobilizes intracellular calcium stores. Increased intracellular calcium and PKC activation further amplify the signaling cascade, leading to the activation of various downstream signaling molecules, including mitogen-activated protein kinases (MAPKs) such as ERK, JNK, and p38. These signaling events ultimately culminate in a range of cellular responses, including chemotaxis, degranulation, phagocytosis, and the production of pro-inflammatory cytokines, such as TNF-α and IL-1β. The IL-8 signaling pathway plays a critical role in orchestrating the immune response to infection and injury. It promotes the recruitment of leukocytes to sites of inflammation, where they can eliminate pathogens and initiate tissue repair. However, dysregulation of this pathway can contribute to chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and chronic obstructive pulmonary disease.'
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Proteins (2)

Compounds (18)