CXCR2

CXCR2 (C-X-C motif chemokine receptor 2), also known as interleukin-8 receptor β (IL8RB) or CD182, is a G protein-coupled receptor (GPCR) that binds ELR+ CXC chemokines including IL-8 (CXCL8) and growth-regulated oncogene-α (GROα/CXCL1). It mediates neutrophil chemotaxis, angiogenesis, and inflammatory responses through activation of Gαi-mediated pathways, triggering downstream MAPK, PI3K/AKT, and β-arrestin signaling cascades. Aberrant CXCR2 activation is implicated in chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, atherosclerosis, and cancer metastasis by promoting leukocyte infiltration and tumor microenvironment remodeling. Several small-molecule antagonists (e.g., AZD5069, navarixin) and monoclonal antibodies targeting CXCR2 or its ligands have reached clinical trials for inflammatory diseases and oncology applications. However, challenges remain in balancing therapeutic efficacy with potential immunosuppressive effects, particularly neutropenia. Recent research explores biased signaling modulation to dissociate anti-inflammatory benefits from adverse effects.