CXCR2, a G-protein-coupled receptor, is one of the 20 chemokine receptors. Its well-known ligands include CXCL8 (IL-8) and CXCL1 (GRO-α). It plays crucial roles in the migration of immune system cells and tumor cells, and is involved in metastasis. It participates in various biological processes such as regulating the actin cytoskeleton, angiogenesis, lymphangiogenesis, and cellular senescence [1].

In animal models, targeting CXCR2 in lung cancer inhibits tumor progression, promotes apoptosis, senescence, and anti-proliferation of lung cancer cells, and enhances the therapeutic effect of cisplatin [2]. In hypertensive retinopathy, CXCR2 knockout (KO) mice show ameliorated symptoms like arteriolar remodelling, macrophage infiltration, and retinal dysfunction, indicating the role of the CXCL1-CXCR2 axis in this disease [3]. In angiotensin II-induced cardiac hypertrophy and remodelling, CXCR2 KO mice and WT mice treated with a CXCR2 inhibitor show attenuated cardiac remodelling and inflammatory response, suggesting that the CXCL1-CXCR2 axis mediates monocyte infiltration in the heart [4].

In conclusion, CXCR2 is a key regulator in multiple biological processes and diseases. Findings from CXCR2 KO mouse models have revealed its significance in cancer, hypertensive retinopathy, and cardiac diseases, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Korbecki, Jan, Kupnicka, Patrycja, Chlubek, Mikołaj, Gutowska, Izabela, Baranowska-Bosiacka, Irena. 2022. CXCR2 Receptor: Regulation of Expression, Signal Transduction, and Involvement in Cancer. In International journal of molecular sciences, 23, . doi:10.3390/ijms23042168. https://pubmed.ncbi.nlm.nih.gov/35216283/

2. Cheng, Yuan, Mo, Fei, Li, Qingfang, Wei, Yuquan, Wei, Xiawei. 2021. Targeting CXCR2 inhibits the progression of lung cancer and promotes therapeutic effect of cisplatin. In Molecular cancer, 20, 62. doi:10.1186/s12943-021-01355-1. https://pubmed.ncbi.nlm.nih.gov/33814009/

3. Wang, Shuai, Bai, Jie, Zhang, Yun-Long, Zhao, Qi, Li, Hui-Hua. 2022. CXCL1-CXCR2 signalling mediates hypertensive retinopathy by inducing macrophage infiltration. In Redox biology, 56, 102438. doi:10.1016/j.redox.2022.102438. https://pubmed.ncbi.nlm.nih.gov/35981418/

4. Wang, Lei, Zhang, Yun-Long, Lin, Qiu-Yue, Du, Jie, Li, Hui-Hua. . CXCL1-CXCR2 axis mediates angiotensin II-induced cardiac hypertrophy and remodelling through regulation of monocyte infiltration. In European heart journal, 39, 1818-1831. doi:10.1093/eurheartj/ehy085. https://pubmed.ncbi.nlm.nih.gov/29514257/