CCL2

CCL2, or chemokine (C-C motif) ligand 2, is a small secreted chemokine of the CC family. In humans it is encoded by the CCL2 gene and is commonly known as monocyte chemoattractant protein-1 (MCP-1).

Function and mechanism: CCL2 acts primarily as a chemotactic factor for monocytes and, to a lesser extent, memory T cells, dendritic cells, and basophils. It is produced by a variety of cell types, including endothelial cells, fibroblasts, macrophages, adipocytes, and smooth muscle cells, in response to inflammatory signals such as IL-1, TNF-α, and lipopolysaccharide. CCL2 binds mainly to the CCR2 receptor to induce leukocyte recruitment to sites of tissue injury or infection; it can also interact with other receptors to a lesser degree.

Regulation and processing: Expression is driven by inflammatory signaling pathways, notably NF-κB. CCL2 is secreted as a mature chemokine after proteolytic processing, and its activity can be influenced by tissue context, glycosaminoglycans, and interactions with other chemokines that shape chemotactic gradients.

Clinical significance: Elevated CCL2 levels are observed in a range of inflammatory and metabolic diseases, including atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, obesity-related insulin resistance, and neurodegenerative disorders such as Alzheimer’s disease. In cancer, CCL2 can recruit tumor-associated macrophages and influence tumor progression in certain settings, and it is studied as a potential biomarker of inflammation.

Therapeutic targeting: The CCL2–CCR2 signaling axis has been explored as a therapeutic target. Approaches include neutralizing antibodies against CCL2 and small-molecule CCR2 antagonists. Clinical results have been mixed; for example, antibodies reducing circulating CCL2 did not yield expected benefit and were followed by rebound increases in CCL2. Ongoing research seeks optimized strategies and defined patient populations, including fibrosis and specific cancers.