Cxcl1-flox Mouse

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 causing the migration and infiltration of neutrophils to the sites of high expression, playing a role in many inflammation-related adverse conditions. Once the CXCL1/CXCR2 axis is activated, multiple downstream pathways can be triggered, such as c-Raf/MAPK/AP-1, p-PKC-μ/p-ILK/NLRP3, JAK2/STAT3, TAK1/NF-κB, etc., which mediate cellular motility state or cell migration [3,4].

In a hypertensive retinopathy (HR) model established by Ang II infusion in mice, Ang II treatment led to a significant elevation in the mRNA levels of Cxcl1 and Cxcr2, along with an increase in the number of CXCR2 + inflammatory cells. However, treatment with a Cxcl1 neutralizing antibody in wild-type mice, or using Cxcr2 knockout (KO) mice and the specific CXCR2 inhibitor SB225002, alleviated arteriolar remodelling, infiltration of Iba1 + macrophages, production of oxidative stress, and retinal dysfunction. These protective effects were related to a reduction in the number of CXCR2 + immune cells, particularly macrophages, and a decrease in pro-inflammatory cytokine expression. Serum Cxcl1 levels and the number of CXCR2 + monocytes/neutrophils were higher in HR patients than in healthy controls, indicating that the CXCL1-CXCR2 axis plays a vital role in the pathogenesis of hypertensive retinopathy [1]. In gastric cancer, CXCL1 induced the accumulation of PMN-MDSCs, which promoted CD8 + T cells exhaustion. The CXCR2 antagonist SB225002 decreased PMN-MDSCs accumulation, increased CD8 + T cells infiltration in gastric cancer, and enhanced the anti-tumor efficacy of anti-PD-1 in tumor-bearing mice [2].

In conclusion, Cxcl1, through its interaction with CXCR2, plays a crucial role in inflammation-related biological processes and disease conditions. The use of Cxcl1-related genetic models, such as Cxcr2 KO mice, has significantly contributed to revealing its role in diseases like hypertensive retinopathy and gastric cancer, providing potential therapeutic targets for these diseases.