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CCL11

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CCL11
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCCL11, SCYA11, C-C motif chemokine ligand 11
External IDsOMIM: 601156; MGI: 103576; HomoloGene: 7929; GeneCards: CCL11; OMA:CCL11 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6356

20292

Ensembl

ENSG00000172156

ENSMUSG00000020676

UniProt

P51671

P48298

RefSeq (mRNA)

NM_002986

NM_011330

RefSeq (protein)

NP_002977

NP_035460

Location (UCSC)Chr 17: 34.29 – 34.29 MbChr 11: 81.95 – 81.95 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6]

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.[7][8][9] 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,[10] CCR3[5] and CCR5.[10] 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.[11]

Clinical significance

Increased CCL11 levels in blood plasma are associated with aging in mice and humans.[12] 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.[12]

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.[13]

It's also a biomarker for CTE or punch-drunk syndrome.[14]

During periods of bone inflammation, CCL11 and CCR3 are upregulated. This is associated with an increase in osteoclast activity.[15]

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[16][17]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000172156 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020676 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Kitaura M, Nakajima T, Imai T, Harada S, Combadiere C, Tiffany HL, Murphy PM, Yoshie O (Mar 1996). "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. doi:10.1074/jbc.271.13.7725. PMID 8631813.
  6. ^ Hein H, Schlüter C, Kulke R, Christophers E, Schröder JM, Bartels J (Aug 1997). "Genomic organization, sequence, and transcriptional regulation of the human eotaxin gene". Biochemical and Biophysical Research Communications. 237 (3): 537–42. doi:10.1006/bbrc.1997.7169. PMID 9299399.
  7. ^ Jose PJ, Griffiths-Johnson DA, Collins PD, Walsh DT, Moqbel R, Totty NF, Truong O, Hsuan JJ, Williams TJ (Mar 1994). "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. doi:10.1084/jem.179.3.881. PMC 2191401. PMID 7509365.
  8. ^ Ponath PD, Qin S, Ringler DJ, Clark-Lewis I, Wang J, Kassam N, Smith H, Shi X, Gonzalo JA, Newman W, Gutierrez-Ramos JC, Mackay CR (Feb 1996). "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. doi:10.1172/JCI118456. PMC 507095. PMID 8609214.
  9. ^ Garcia-Zepeda EA, Rothenberg ME, Ownbey RT, Celestin J, Leder P, Luster AD (Apr 1996). "Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia". Nature Medicine. 2 (4): 449–56. doi:10.1038/nm0496-449. PMID 8597956. S2CID 25571283.
  10. ^ a b Ogilvie P, Bardi G, Clark-Lewis I, Baggiolini M, Uguccioni M (Apr 2001). "Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5". Blood. 97 (7): 1920–4. doi:10.1182/blood.V97.7.1920. PMID 11264152.
  11. ^ Baggiolini M, Dewald B, Moser B (1997). "Human chemokines: an update". Annual Review of Immunology. 15: 675–705. doi:10.1146/annurev.immunol.15.1.675. PMID 9143704.
  12. ^ a b Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, et al. (Sep 2011). "The ageing systemic milieu negatively regulates neurogenesis and cognitive function". Nature. 477 (7362): 90–4. Bibcode:2011Natur.477...90V. doi:10.1038/nature10357. PMC 3170097. PMID 21886162.
  13. ^ Fernandez-Egea E, Scoriels L, Theegala S, Giro M, Ozanne SE, Burling K, Jones PB (Oct 2013). "Cannabis use is associated with increased CCL11 plasma levels in young healthy volunteers". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 46: 25–8. doi:10.1016/j.pnpbp.2013.06.011. PMID 23820464. S2CID 207410464.
  14. ^ Cherry JD, Stein TD, Tripodis Y, Alvarez VE, Huber BR, Au R, Kiernan PT, Daneshvar DH, Mez J, Solomon TM, Alosco ML, McKee AC (2017). "CCL11 is increased in the CNS in chronic traumatic encephalopathy but not in Alzheimer's disease". PLOS ONE. 12 (9): e0185541. Bibcode:2017PLoSO..1285541C. doi:10.1371/journal.pone.0185541. PMC 5614644. PMID 28950005.
  15. ^ Kindstedt E, Holm CK, Sulniute R, Martinez-Carrasco I, Lundmark R, Lundberg P (July 2017). "CCL11, a novel mediator of inflammatory bone resorption". Scientific Reports. 7 (1): 5334. Bibcode:2017NatSR...7.5334K. doi:10.1038/s41598-017-05654-w. PMC 5509729. PMID 28706221.
  16. ^ 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. PMC 9189143. PMID 35768006.
  17. ^ 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. PMC 8764721. PMID 35043113.

Further reading

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