Chemokine ligand 2, also known as CCL2, which is also referred to as ‘monocyte chemoattractant protein 1 or MCP1 and also ‘small inducible cytokine A2’, is a small cytokine that is part of the CC chemokine family. CCL2 is known to recruit monocytes, memory T cells, and dendritic cells to areas of inflammation which has been caused by a tissue injury or an infection.
Where is CCL2 located?
In human genomes, CCL2 and various other CC chemokines are found on chromosome 17. The gene span of this is 1927 bases with the CCL2 gene residing on the Watson strand. The CCL2 gene is made up of three exons and two introns, and the protein precursor is made up of a signal peptide of 23 amino acids. Whereas, the mature version of CCL2 is made up of 76 amino acids in length.
What about in the human population?
Usually, in human the levels of CCL2 vary widely depending on a range of factors. In white people with European descent, the multivariable heritability of CCL2 concentrations is around 0.37 in blood plasma and 0.44 in the blood serum.
CCL2 is a monomeric polypeptide, which has a molecular weight of 13 kDa. CCL2 is stuck to the plasma membrane of the endothelial cells and is linked by glycosaminoglycan chains of proteoglycans. It’s monocytes, macrophages, and dendritic cells that primarily secrete CCL2. In terms of what induces the CCL2 gene, it’s the platelet derived growth factor that is the major inducer. However, to become activated, CCL2 protein has to be split by metalloproteinase MMP-12.
CCL2 is a vital part of the pathogenesis of various disease characterized by monocytic infiltrates, including arthritis (rheumatoid), psorosis, and atherosclerosis. It has been found that administration of anti-CCL2 antibodies in a model of glomerulonephritis can reduce the infiltration of macrophages and T-cells, which can reduce crescent formation, in addition to scarring and renal problems.
CCL2 is also involved in the processes that are part of various diseases of the central nervous system, and which have neuronal degeneration. Studies have found that CCL2 expression in glial cells is boosted in epilepsy, Alzheimer’s disease, brain ischemia, and traumatic brain injury.
Adipocytes release a range of adipokines that could be included in negative cross-talk between adipose tissue and skeletal muscle. CCL2 can impair insulin signaling in skeletal muscle cells via ERK1/2 activation when doses that are similar to physiological plasma concentrations, but doesn’t involve activation of Nf-kB pathway. CCL2 can dramatically reduce insulin-stimulated glucose uptake in the myocyte cells. CCL2 could suggest a molecular link in the negative cross-talk between adipose tissue and skeletal muscle.
Use of HL-1 cardiomyocytes and human myocytes with oxidized-LDL induced the expression of BNP and CCL2 genes, while the native LDL tends to have no effect.
Use of melatonin in older mice with age related liver inflammation decrease the mRNA expression of TNF, IL1B, HO, and NKAP in older male mice. The protein expression of TNF-g was also decreased in size.