Cxcl5, also known as C-X-C motif chemokine ligand 5, is a member of the chemokine family. It binds to CXCR2, a G-protein coupled receptor, and plays a crucial role in inflammation-related processes. It is involved in recruiting and activating chemotactic cells, participating in angiogenesis, and regulating the tumor microenvironment [1,2].

In various disease models, the role of Cxcl5 has been elucidated. In gouty arthritis model mice, increased Cxcl5 expression in ankle joints activates CXCR2 on nociceptive sensory neurons, triggering pain and inflammation [3]. In colorectal cancer, tumor-derived Cxcl5 promotes metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways [4]. In chronic cerebral ischemia, astrocytic Cxcl5 hinders microglial phagocytosis of myelin debris and aggravates white matter injury, as shown in astrocytic Cxcl5 conditional knockout (cKO) mice [5]. In diabetes mellitus, suppressing Cxcl5 in knockout mice recovers neovascularization and accelerates wound healing [6].

In conclusion, Cxcl5 is essential in inflammation-associated biological processes. Studies using gene knockout and conditional knockout mouse models have revealed its roles in diseases such as gouty arthritis, colorectal cancer, chronic cerebral ischemia, and diabetes mellitus. These findings provide insights into the potential of Cxcl5 as a therapeutic target for these diseases.

References:

1. Zhang, Wen, Wang, Huishan, Sun, Mingyang, You, Qiang, Miao, Lin. . CXCL5/CXCR2 axis in tumor microenvironment as potential diagnostic biomarker and therapeutic target. In Cancer communications (London, England), 40, 69-80. doi:10.1002/cac2.12010. https://pubmed.ncbi.nlm.nih.gov/32237072/

2. Deng, Jie, Jiang, Rongqi, Meng, Enqing, Wu, Hao. 2022. CXCL5: A coachman to drive cancer progression. In Frontiers in oncology, 12, 944494. doi:10.3389/fonc.2022.944494. https://pubmed.ncbi.nlm.nih.gov/35978824/

3. Yin, Chengyu, Liu, Boyu, Dong, Zishan, Wang, Chuan, Liu, Boyi. 2024. CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis. In Nature communications, 15, 3263. doi:10.1038/s41467-024-47640-7. https://pubmed.ncbi.nlm.nih.gov/38627393/

4. Zhao, Jingkun, Ou, Baochi, Han, Dingpei, Feng, Hao, Lu, Aiguo. 2017. Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways. In Molecular cancer, 16, 70. doi:10.1186/s12943-017-0629-4. https://pubmed.ncbi.nlm.nih.gov/28356111/

5. Cao, Qian, Chen, Jian, Zhang, Zhi, Xu, Yun, Qiu, Shuwei. 2023. Astrocytic CXCL5 hinders microglial phagocytosis of myelin debris and aggravates white matter injury in chronic cerebral ischemia. In Journal of neuroinflammation, 20, 105. doi:10.1186/s12974-023-02780-3. https://pubmed.ncbi.nlm.nih.gov/37138312/

6. Chen, Ching, Lin, Liang-Yu, Chen, Jaw-Wen, Chang, Ting-Ting. 2023. CXCL5 suppression recovers neovascularization and accelerates wound healing in diabetes mellitus. In Cardiovascular diabetology, 22, 172. doi:10.1186/s12933-023-01900-w. https://pubmed.ncbi.nlm.nih.gov/37420254/