CCL2
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Location (UCSC) | Chr 17: 34.26 – 34.26 Mb | Chr 11: 81.99 – 81.99 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
The chemokine (C-C motif) ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. CCL2 is a small
Genomics
In the human genome, CCL2 and many other CC chemokines are located on chromosome 17 (17q11.2-q21.1).[8] The gene span is 1,927 bases and the CCL2 gene resides on the Watson (plus) strand. The CCL2 gene has three exons and two introns. The CCL2 protein precursor contains a signal peptide of 23 amino acids. In turn, the mature CCL2 is 76 amino acids long.[9][10] The CCL2 predicted weight is 11.025 kilodaltons (kDa).
Population genetics
In humans, the levels of CCL2 can vary considerably. In the white people of European descent, the multivariable-adjusted heritability of CCL2 concentrations is as much as 0.37 in the blood plasma and 0.44 - in the serum.[11][12]
Molecular biology
CCL2 is a monomeric
CCR2 and CCR4 are two cell surface receptors that bind CCL2.[14]
CCL2 exhibits a chemotactic activity for monocytes and basophils. However, it does not attract neutrophils or eosinophils. After deletion of the N-terminal residue, CCL2 loses its attractivity for basophils and becomes a chemoattractant of eosinophils. Basophils and mast cells that are treated with CCL2 release their granules to the intercellular space. This effect can be also potentiated by a pre-treatment with IL-3 or even by other cytokines.[15][16] CCL2 augments monocyte anti-tumor activity and it is essential for formation of granulomas. CCL2 protein become a CCR2 antagonist when it is cleaved by metalloproteinase MMP-12.[17]
CCL2 can be found at the sites of tooth eruption and bone degradation. In the bone, CCL2 is expressed by mature
The CCL2 chemokine is also expressed by neurons, astrocytes and microglia. The expression of CCL2 in neurons is mainly found in the cerebral cortex, globus pallidus, hippocampus, paraventricular and supraoptic hypothalamic nuclei, lateral hypothalamus, substantia nigra, facial nuclei, motor and spinal trigeminal nuclei, gigantocellular reticular nucleus and in Purkinje cells in the cerebellum.[19]
Clinical importance
CCL2 is implicated in pathogeneses of several diseases characterized by monocytic infiltrates, such as psoriasis, rheumatoid arthritis and atherosclerosis.[20]
Administration of anti-CCL2 antibodies in a model of glomerulonephritis reduces infiltration of macrophages and T cells, reduces crescent formation, as well as scarring and renal impairment.[21]
CCL2 is involved in the neuroinflammatory processes that takes place in the various diseases of the central nervous system (CNS), which are characterized by neuronal degeneration.
Hypomethylation of CpG sites within the CCL2 promoter region is affected by high levels of blood glucose and TG, which increase CCL2 levels in the blood serum. The later plays an important role in the vascular complications of type 2 diabetes.[29]
CCL2 induces
Incubation of HL-1
Treatment with melatonin in old mice with age related liver inflammation decreased the mRNA expression of
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000108691 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035352 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 34988399.
- PMID 8170963.
- S2CID 24481789.
- PMID 2004761.
- S2CID 7097272.
- PMID 2923622.
- S2CID 12320863.
- S2CID 8242432.
- PMID 29375123.
- S2CID 24366011.
- PMID 8550082.
- PMID 1569397.
- S2CID 25944573.
- S2CID 22756184.
- S2CID 22254007.
- S2CID 45028620.
- PMID 9104823.
- S2CID 28336866.
- PMID 20034406.
- S2CID 5121343.
- S2CID 45538922.
- PMID 20205643.
- S2CID 13552110.
- PMID 20029451.
- S2CID 14613351.
- PMID 21589925.
- PMID 16439461.
- S2CID 9801961.
- S2CID 42491323.
External links
- Human CCL2 genome location and CCL2 gene details page in the UCSC Genome Browser.
Further reading
- Yoshimura T, Leonard EJ (1991). "Human Monocyte Chemoattractant Protein-1 (MCP-1)". Chemotactic Cytokines. Advances in Experimental Medicine and Biology. Vol. 305. pp. 47–56. PMID 1661560.
- Wahl SM, Greenwell-Wild T, Hale-Donze H, Moutsopoulos N, Orenstein JM (September 2000). "Permissive factors for HIV-1 infection of macrophages". Journal of Leukocyte Biology. 68 (3): 303–10. S2CID 41684404.
- Sell H, Eckel J (June 2007). "Monocyte chemotactic protein-1 and its role in insulin resistance". Current Opinion in Lipidology. 18 (3): 258–62. S2CID 33827660.