Cxcl1, also known as growth-regulated gene-α (GRO-α) or melanoma growth-stimulatory activity (MGSA), is a cytokine belonging to the CXC sub-family of chemokines. Its main receptor is CXC motif chemokine receptor 2 (CXCR2). Cxcl1 is involved in the migration and infiltration of neutrophils to high-expression sites, playing a role in inflammation-related processes. Once the Cxcl1/CXCR2 axis is activated, multiple downstream pathways like c-Raf/MAPK/AP-1, p-PKC-μ/p-ILK/NLRP3, JAK2/STAT3, TAK1/NF-κB can be triggered, mediating cellular motility or migration [3].

In a hypertensive retinopathy (HR) model established by Ang II infusion, Cxcl1 mRNA levels increased, and treatment with a Cxcl1 neutralizing antibody reduced Ang II-induced central retinal thickness increase, arteriolar remodelling, superoxide production, and retinal dysfunction in wild-type mice. CXCR2 knockout (KO) mice also showed ameliorated symptoms of arteriolar remodelling, macrophage infiltration, oxidative stress, and retinal dysfunction, suggesting Cxcl1-CXCR2 signalling mediates HR by inducing macrophage infiltration [1]. In gastric cancer, CXCL1 induced PMN-MDSCs accumulation, which promoted CD8+ T cells exhaustion. The CXCR2 antagonist SB225002 decreased PMN-MDSCs accumulation and enhanced anti-tumor efficacy of anti-PD-1 in tumor-bearing mice [2].

In conclusion, Cxcl1 plays a crucial role in inflammation-related biological processes. Gene knockout models, especially CXCR2 KO mice, have revealed its significant involvement in diseases such as hypertensive retinopathy and gastric cancer, providing potential therapeutic targets for these diseases.

References:

1. 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/

2. Zhou, Xingyu, Fang, Deliang, Liu, Haohan, He, Yulong, Xu, Jianbo. 2022. PMN-MDSCs accumulation induced by CXCL1 promotes CD8+ T cells exhaustion in gastric cancer. In Cancer letters, 532, 215598. doi:10.1016/j.canlet.2022.215598. https://pubmed.ncbi.nlm.nih.gov/35176418/

3. Jiang, Suli, Liang, Jie, Li, Wei, Zhang, Li, Zhang, Bei. 2023. The role of CXCL1/CXCR2 axis in neurological diseases. In International immunopharmacology, 120, 110330. doi:10.1016/j.intimp.2023.110330. https://pubmed.ncbi.nlm.nih.gov/37247498/