Ccl2, also known as monocytic chemotactic protein 1 (MCP-1), is an integral chemotactic factor belonging to the CC chemokine family. It recruits macrophages for the immune response by binding to its receptors such as CCR2, ACKR1, and ACKR2, and thus participates in multiple biological processes including inflammation, tissue remodeling, and angiogenesis [2,8].

The CCL2-CCR2 axis has been implicated in numerous disease conditions. In cardiovascular diseases like heart failure, atherosclerosis, and hypertension, laboratory data suggest its role in the disease development and progression, yet clinical translation remains a challenge [1]. In normal and pathological pregnancies, abnormal CCL2 levels are associated with adverse outcomes such as spontaneous abortion and preeclampsia [2]. In cancer, the activation of the CCL2/CCR2 axis promotes the migration of macrophages with an immune-suppressive phenotype, cancer progression, and metastasis [3,4,7]. Also, in obesity and metabolic diseases, this axis influences the genesis and progression of metabolic syndrome [6]. In neuropathic pain, a nerve injury-specific lncRNA promotes pain by increasing Ccl2 expression [5]. In cerebral ischemia-reperfusion injury, CCL2/CCR2 is involved in the pathological process, with increased expression in the acute phase promoting neuroinflammation and in the later phase participating in neuroblast migration [9].

In conclusion, Ccl2 is crucial in immune-related processes and inflammation. Through studies, mainly in various disease models, the CCL2-CCR2 axis has been shown to play significant roles in cardiovascular diseases, pregnancy-related disorders, cancer, obesity-related metabolic diseases, neuropathic pain, and cerebral ischemia-reperfusion injury. These findings from different disease models help in understanding the functions of Ccl2 and potentially developing targeted therapies.

References:

1. Zhang, Haixia, Yang, Ke, Chen, Feng, Li, Lan, Fan, Guanwei. 2022. Role of the CCL2-CCR2 axis in cardiovascular disease: Pathogenesis and clinical implications. In Frontiers in immunology, 13, 975367. doi:10.3389/fimmu.2022.975367. https://pubmed.ncbi.nlm.nih.gov/36110847/

2. Lin, Zhi, Shi, Jia-Lu, Chen, Min, Li, Ming-Qing, Shao, Jun. 2023. CCL2: An important cytokine in normal and pathological pregnancies: A review. In Frontiers in immunology, 13, 1053457. doi:10.3389/fimmu.2022.1053457. https://pubmed.ncbi.nlm.nih.gov/36685497/

3. Hao, Qiongyu, Vadgama, Jaydutt V, Wang, Piwen. 2020. CCL2/CCR2 signaling in cancer pathogenesis. In Cell communication and signaling : CCS, 18, 82. doi:10.1186/s12964-020-00589-8. https://pubmed.ncbi.nlm.nih.gov/32471499/

4. Pozzi, Sabina, Satchi-Fainaro, Ronit. 2024. The role of CCL2/CCR2 axis in cancer and inflammation: The next frontier in nanomedicine. In Advanced drug delivery reviews, 209, 115318. doi:10.1016/j.addr.2024.115318. https://pubmed.ncbi.nlm.nih.gov/38643840/

5. Du, Shibin, Wu, Shaogen, Feng, Xiaozhou, Davidson, Steve, Tao, Yuan-Xiang. . A nerve injury-specific long noncoding RNA promotes neuropathic pain by increasing Ccl2 expression. In The Journal of clinical investigation, 132, . doi:10.1172/JCI153563. https://pubmed.ncbi.nlm.nih.gov/35775484/

6. Wu, Yue, Ma, Yanchun. 2024. CCL2-CCR2 signaling axis in obesity and metabolic diseases. In Journal of cellular physiology, 239, e31192. doi:10.1002/jcp.31192. https://pubmed.ncbi.nlm.nih.gov/38284280/

7. Kadomoto, Suguru, Izumi, Kouji, Mizokami, Atsushi. 2021. Roles of CCL2-CCR2 Axis in the Tumor Microenvironment. In International journal of molecular sciences, 22, . doi:10.3390/ijms22168530. https://pubmed.ncbi.nlm.nih.gov/34445235/

8. Singh, Sanjiv, Anshita, D, Ravichandiran, V. 2021. MCP-1: Function, regulation, and involvement in disease. In International immunopharmacology, 101, 107598. doi:10.1016/j.intimp.2021.107598. https://pubmed.ncbi.nlm.nih.gov/34233864/

9. Geng, Huixia, Chen, Luna, Tang, Jing, Chen, Yi'ang, Wang, Lai. 2022. The Role of CCL2/CCR2 Axis in Cerebral Ischemia-Reperfusion Injury and Treatment: From Animal Experiments to Clinical Trials. In International journal of molecular sciences, 23, . doi:10.3390/ijms23073485. https://pubmed.ncbi.nlm.nih.gov/35408846/