Biology:CCL11

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Short description: Mammalian protein found in Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

C-C motif chemokine 11 also known as eosinophil chemotactic protein and eotaxin-1 is a protein that in humans is encoded by the CCL11 gene. This gene is encoded on three exons and is located on chromosome 17.[1][2]

Function

CCL11 is a small cytokine belonging to the CC chemokine family. CCL11 selectively recruits eosinophils by inducing their chemotaxis, and therefore, is implicated in allergic responses.[3][4][5] The effects of CCL11 are mediated by its binding to a G-protein-linked receptor known as a chemokine receptor. Chemokine receptors for which CCL11 is a ligand include CCR2,[6] CCR3[1] and CCR5.[6] However, it has been found that eotaxin-1 (CCL11) has high degree selectivity for its receptor, such that they are inactive on neutrophils and monocytes, which do not express CCR3.[7]

Clinical significance

Increased CCL11 levels in blood plasma are associated with aging in mice and humans.[8] Additionally, it has been demonstrated that exposing young mice to CCL11 or the blood plasma of older mice decreases their neurogenesis and cognitive performance on behavioural tasks thought to be dependent on neurogenesis in the hippocampus.[8]

Higher plasma concentrations of CCL11 have been found in current cannabis users compared to past users and those who had never used. CCL11 has also been found in higher concentrations in people with schizophrenia; cannabis is a known trigger of schizophrenia.[9]

It's also a biomarker for CTE or punch-drunk syndrome.[10]

During periods of bone inflammation, CCL11 and CCR3 are upregulated. This is associated with an increase in osteoclast activity.[11]

In 2022, Monje et al demonstrated that elevated levels of CCL11 may contribute to the brain fog associated with both chemotherapy and so-called Long Covid[12][13]

References

  1. ↑ 1.0 1.1 "Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3". The Journal of Biological Chemistry 271 (13): 7725–30. Mar 1996. doi:10.1074/jbc.271.13.7725. PMID 8631813. 
  2. ↑ "Genomic organization, sequence, and transcriptional regulation of the human eotaxin gene". Biochemical and Biophysical Research Communications 237 (3): 537–42. Aug 1997. doi:10.1006/bbrc.1997.7169. PMID 9299399. 
  3. ↑ "Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation". The Journal of Experimental Medicine 179 (3): 881–7. Mar 1994. doi:10.1084/jem.179.3.881. PMID 7509365. 
  4. ↑ "Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils". The Journal of Clinical Investigation 97 (3): 604–12. Feb 1996. doi:10.1172/JCI118456. PMID 8609214. 
  5. ↑ "Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia". Nature Medicine 2 (4): 449–56. Apr 1996. doi:10.1038/nm0496-449. PMID 8597956. 
  6. ↑ 6.0 6.1 "Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5". Blood 97 (7): 1920–4. Apr 2001. doi:10.1182/blood.V97.7.1920. PMID 11264152. 
  7. ↑ "Human chemokines: an update". Annual Review of Immunology 15: 675–705. 1997. doi:10.1146/annurev.immunol.15.1.675. PMID 9143704. 
  8. ↑ 8.0 8.1 "The ageing systemic milieu negatively regulates neurogenesis and cognitive function". Nature 477 (7362): 90–4. Sep 2011. doi:10.1038/nature10357. PMID 21886162. Bibcode: 2011Natur.477...90V. 
  9. ↑ "Cannabis use is associated with increased CCL11 plasma levels in young healthy volunteers". Progress in Neuro-Psychopharmacology & Biological Psychiatry 46: 25–8. Oct 2013. doi:10.1016/j.pnpbp.2013.06.011. PMID 23820464. 
  10. ↑ "CCL11 is increased in the CNS in chronic traumatic encephalopathy but not in Alzheimer's disease". PLOS ONE 12 (9): e0185541. 2017. doi:10.1371/journal.pone.0185541. PMID 28950005. Bibcode: 2017PLoSO..1285541C. 
  11. ↑ "CCL11, a novel mediator of inflammatory bone resorption". Scientific Reports 7 (1): 5334. July 2017. doi:10.1038/s41598-017-05654-w. PMID 28706221. Bibcode: 2017NatSR...7.5334K. 
  12. ↑ Fernández-Castañeda, A. et al. (2022). "Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation". Cell 185 (14): 2452–2468.e16. doi:10.1016/j.cell.2022.06.008. PMID 35768006. 
  13. ↑ Fernández-Castañeda, A. et al. (2022). "Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain". BioRxiv: The Preprint Server for Biology. doi:10.1101/2022.01.07.475453. PMID 35043113. 

External links

Further reading



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