CCL1

Last updated

chemokine (C-C motif) ligand 1
Identifiers
SymbolCCL1
Alt. symbolsSCYA1, I-309, TCA3, P500, SISe
NCBI gene 6346
HGNC 10609
OMIM 182281
PDB 1EL0
RefSeq NM_002981
UniProt P22362
Other data
Locus Chr. 17 q11.2
Search for
Structures Swiss-model
Domains InterPro

Chemokine (C-C motif) ligand 1 (CCL1) is also known as small inducible cytokine A1 and I-309 in humans. CCL1 is a small glycoprotein that belongs to the CC chemokine family.

Contents

Genomics

CCL1 is encoded by CCL1 gene which is one of the several chemokine genes clustered on the chromosome 17q11.2-q12 in humans. [1] It is expressed by specifically activated T cells upon secondary stimulation. [2] The homologous mouse gene is termed Tca-3.

Discovery

CCL is the first human CCL chemokine that was identified by molecular cloning during searching for genes expressed by T cells. [3]

Function

CCL1 is a small glycoprotein with a molecular weight of approximately 15-16 kDa. [2] CCL1 is secreted by activated monocytes/macrophages, T lymphocytes and endothelial cells. [2] [4] CCL1 binds to the chemokine receptor CCR8 and induces Ca2+ influx, chemotaxis and regulate apoptosis. [5] CCR8 is constitutively expressed in monocytes/macrophages, Th2, and regulatory T lymphocytes. [6] [7] [1] Thus, CCL1 mainly acts as a chemoattractant for monocytes/macrophages, T lymphocytes, specially Th2-differentiated T cells and a subset of T regulatory cells in vitro into inflammatory site. It can also attract NK cells, immature B cells but does not attract neutrophils. [2]

CCL1 stimulates a transient increase in the concentration of cytoplasmic free calcium in monocytes but not in other type of cells. [2] Furthermore, CCL1 inhibits apoptosis in thymic cell lines by the RAS/MAPK pathway but can prevent dexamethasone-induced apoptosis in cultured murine thymic lymphoma cells. [8] [9] [5]

Clinical importance

CCL1 is involved in inflammatory processes through leukocyte recruitment and could play a crucial role in angiogenesis and other viral and tumoral processes. [10] [11] [12] For example, CCL1 transcription was increased in primary human CD4+ T cells expressing T cell immunoglobulin and protein 3 containing the mucin domain (TIM-3) and was identified as a differentially transcribed gene in CD4+ cells T cells expressing TIM-3 that play a role in the regulation anti-tumor immunity. [6] CCL1 is also overexpressed in ATL cells and mediates an autocrine antiapoptotic loop along CCR8 for in vivo growth and survival of leukemic cells. [11] Due to these facts, the dysregulation of CCL1 can leads in pathogenesis of several diseases. Some single nucleotide polymorphisms (SNPs) in the CCL1 gene are associated with exacerbations of chronic obstructive pulmonary disease (COPD). [13]

CCL1 plays a role in various CNS functions and could be associated with some neuroinflammatory disorders. In addition to other chemokines, such as CCL2, CCL3, and CCL4, the presence of CCL1 has been reported in the development of brain abscesses, most likely leading to an influx of lymphocytes and monocytes and thus to an adaptive immune response. [14]

Because CCL1 binds to the CCR8 receptor, some diseases can be caused by dysregulation and dysfunction of this receptor. For example, CCL1 and CCR8 mRNA expression has been detected in the CNS of mice with experimental autoimmune encephalomyelitis (EAE). [15] However, the CCR8 receptor has also been shown to be associated with phagocytic macrophages and activated microglia in MS lesions and directly correlate with demyelinating activity. [6] The CCR8 receptor can serve as a basic receptor for various strains of HIV-1 tropical, dual-tropical and macrophage tropics of HIV-1. Thus, CCl1 has also been studied as a possible potent inhibitor of fusion of cells and cells mediated by HIV-1 envelope and viral infection. [16]

Due to the pathologies that can be caused by dysregulation of the CCR8 receptor, some research are focused on the possibilities of inhibiting this receptor. To suppress the apoptotic activity of CCL1, removing three amino acids from the C-terminus of CCL1 reduces CCR8 binding but converts CCL1 to a more potent CCR8 agonist, leading to increased intracellular calcium release and increased antiapoptotic activity. [17]

Related Research Articles

<span class="mw-page-title-main">Interleukin 9</span> Protein-coding gene in the species Homo sapiens

Interleukin 9, also known as IL-9, is a pleiotropic cytokine belonging to the group of interleukins. IL-9 is produced by variety of cells like mast cells, NKT cells, Th2, Th17, Treg, ILC2, and Th9 cells in different amounts. Among them, Th9 cells are regarded as the major CD4+ T cells that produce IL-9.

<span class="mw-page-title-main">CCL5</span> Mammalian protein found in humans

Chemokine ligand 5 is a protein which in humans is encoded by the CCL5 gene. The gene has been discovered in 1990 by in situ hybridisation and it is localised on 17q11.2-q12 chromosome.

<span class="mw-page-title-main">CCL7</span> Mammalian protein found in Homo sapiens

Chemokine ligand 7 (CCL7) is a small cytokine that was previously called monocyte-chemotactic protein 3 (MCP3). CCL7 is a small protein that belongs to the CC chemokine family and is most closely related to CCL2.

<span class="mw-page-title-main">CCL20</span> Mammalian protein found in Homo sapiens

Chemokine ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly attracts neutrophils. CCL20 is implicated in the formation and function of mucosal lymphoid tissues via chemoattraction of lymphocytes and dendritic cells towards the epithelial cells surrounding these tissues. CCL20 elicits its effects on its target cells by binding and activating the chemokine receptor CCR6.

<span class="mw-page-title-main">CCL18</span> Mammalian protein found in Homo sapiens

Chemokine ligand 18 (CCL18) is a small cytokine belonging to the CC chemokine family. The functions of CCL18 have been well studied in laboratory settings, however the physiological effects of the molecule in living organisms have been difficult to characterize because there is no similar protein in rodents that can be studied. The receptor for CCL18 has been identified in humans only recently, which will help scientists understand the molecule's role in the body.

<span class="mw-page-title-main">CCL21</span> Mammalian protein found in Homo sapiens

Chemokine ligand 21 (CCL21) is a small cytokine belonging to the CC chemokine family. This chemokine is also known as 6Ckine, exodus-2, and secondary lymphoid-tissue chemokine (SLC). CCL21 elicits its effects by binding to a cell surface chemokine receptor known as CCR7. The main function of CCL21 is to guide CCR7 expressing leukocytes to the secondary lymphoid organs, such as lymph nodes and Peyer´s patches.

<span class="mw-page-title-main">CCL22</span> Mammalian protein found in Homo sapiens

C-C motif chemokine 22 is a protein that in humans is encoded by the CCL22 gene.

<span class="mw-page-title-main">CCL17</span> Mammalian protein found in Homo sapiens

CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an immune response. However, in other cancers, such as melanoma, an increase in CCL17 is linked to an improved outcome. CCL17 has also been linked to autoimmune and allergic diseases.

<span class="mw-page-title-main">CXCL9</span> Mammalian protein found in Homo sapiens

Chemokine ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as monokine induced by gamma interferon (MIG). The CXCL9 is one of the chemokine which plays role to induce chemotaxis, promote differentiation and multiplication of leukocytes, and cause tissue extravasation.

CC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins since they span the cell membrane seven times. To date, ten true members of the CC chemokine receptor subfamily have been described. These are named CCR1 to CCR10 according to the IUIS/WHO Subcommittee on Chemokine Nomenclature.

Chemokine ligand 17 (CXCL17) is a small cytokine belonging to the CXC chemokine family that has been identified in humans and mice. CXCL17 attracts dendritic cells and monocytes and is regulated in tumors. It is also known as VEGF co-regulated chemokine 1 (VCC-1) and dendritic cell- and monocyte-attracting chemokine-like protein (DMC). This chemokine is constitutively expressed in the lung. The gene for human CXCL17 is located on chromosome 19.

CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, macrophages, and certain T cells. CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction. The most well-researched membrane receptor implicated in triggering lysis by NK cells, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC). It can be used to isolate populations of specific immune cells through fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting, using antibodies directed towards CD16.

<span class="mw-page-title-main">C-C chemokine receptor type 7</span> Protein-coding gene in the species Homo sapiens

C-C chemokine receptor type 7 is a protein that in humans is encoded by the CCR7 gene. Two ligands have been identified for this receptor: the chemokines ligand 19 (CCL19/ELC) and ligand 21 (CCL21). The ligands have similar affinity for the receptor, though CCL19 has been shown to induce internalisation of CCR7 and desensitisation of the cell to CCL19/CCL21 signals. CCR7 is a transmembrane protein with 7 transmembrane domains, which is coupled with heterotrimeric G proteins, which transduce the signal downstream through various signalling cascades. The main function of the receptor is to guide immune cells to immune organs by detecting specific chemokines, which these tissues secrete.

<span class="mw-page-title-main">CCR1</span> Protein in humans

C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.

<span class="mw-page-title-main">C-C chemokine receptor type 6</span> Mammalian protein found in Homo sapiens

Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene. CCR6 has also recently been designated CD196. The gene is located on the long arm of Chromosome 6 (6q27) on the Watson (plus) strand. It is 139,737 bases long and encodes a protein of 374 amino acids.

<span class="mw-page-title-main">CD83</span> Human protein

CD83 is a human protein encoded by the CD83 gene.

<span class="mw-page-title-main">CCR8 (gene)</span> Protein-coding gene in the species Homo sapiens

Chemokine receptor 8, also known as CCR8, is a protein which in humans is encoded by the CCR8 gene. CCR8 has also recently been designated CDw198.

<span class="mw-page-title-main">CCR9</span> Protein-coding gene in the species Homo sapiens

C-C chemokine receptor type 9 is a protein that in humans is encoded by the CCR9 gene. This gene is mapped to the chemokine receptor gene cluster region. Two alternatively spliced transcript variants have been described.

C-C motif chemokine 4-like is a protein that in humans is encoded by the CCL4L1 gene.

<span class="mw-page-title-main">FCGR2B</span>

Fc fragment of IgG receptor IIb is a low affinity inhibitory receptor for the Fc region of immunoglobulin gamma (IgG). FCGR2B participates in the phagocytosis of immune complexes and in the regulation of antibody production by B lymphocytes.

References

  1. 1 2 Rollins BJ (August 1997). "Chemokines". Blood. 90 (3): 909–28. doi: 10.1182/blood.V90.3.909 . PMID   9242519.
  2. 1 2 3 4 5 Miller MD, Krangel MS (April 1992). "The human cytokine I-309 is a monocyte chemoattractant". Proceedings of the National Academy of Sciences of the United States of America. 89 (7): 2950–4. Bibcode:1992PNAS...89.2950M. doi: 10.1073/pnas.89.7.2950 . PMC   48781 . PMID   1557400.
  3. ↑ Miller MD, Wilson SD, Dorf ME, Seuanez HN, O'Brien SJ, Krangel MS (October 1990). "Sequence and chromosomal location of the I-309 gene. Relationship to genes encoding a family of inflammatory cytokines". Journal of Immunology. 145 (8): 2737–44. doi: 10.4049/jimmunol.145.8.2737 . PMID   2212659.
  4. ↑ Wilson SD, Burd PR, Billings PR, Martin CA, Dorf ME (September 1988). "The expression and regulation of a potential lymphokine gene (TCA3) in CD4 and CD8 T cell clones". Journal of Immunology. 141 (5): 1563–70. doi: 10.4049/jimmunol.141.5.1563 . PMID   2457620.
  5. 1 2 Tiffany HL, Lautens LL, Gao JL, Pease J, Locati M, Combadiere C, et al. (July 1997). "Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309". The Journal of Experimental Medicine. 186 (1): 165–70. doi: 10.1084/jem.186.1.165 . PMC   2198957 . PMID   9207005.
  6. 1 2 3 Trebst C, Staugaitis SM, Kivisäkk P, Mahad D, Cathcart MK, Tucky B, et al. (February 2003). "CC chemokine receptor 8 in the central nervous system is associated with phagocytic macrophages". The American Journal of Pathology. 162 (2): 427–38. doi:10.1016/S0002-9440(10)63837-0. PMC   1851139 . PMID   12547701.
  7. ↑ Zingoni A, Soto H, Hedrick JA, Stoppacciaro A, Storlazzi CT, Sinigaglia F, et al. (July 1998). "The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells". Journal of Immunology. 161 (2): 547–51. doi: 10.4049/jimmunol.161.2.547 . PMID   9670926.
  8. ↑ Louahed J, Struyf S, Demoulin JB, Parmentier M, Van Snick J, Van Damme J, Renauld JC (February 2003). "CCR8-dependent activation of the RAS/MAPK pathway mediates anti-apoptotic activity of I-309/ CCL1 and vMIP-I". European Journal of Immunology. 33 (2): 494–501. doi: 10.1002/immu.200310025 . PMID   12645948.
  9. ↑ Van Snick J, Houssiau F, Proost P, Van Damme J, Renauld JC (September 1996). "I-309/T cell activation gene-3 chemokine protects murine T cell lymphomas against dexamethasone-induced apoptosis". Journal of Immunology. 157 (6): 2570–6. doi: 10.4049/jimmunol.157.6.2570 . PMID   8805659.
  10. ↑ Tamgüney G, Van Snick J, Fickenscher H (November 2004). "Autocrine stimulation of rhadinovirus-transformed T cells by the chemokine CCL1/I-309". Oncogene. 23 (52): 8475–85. doi: 10.1038/sj.onc.1207903 . PMID   15378023.
  11. 1 2 Ruckes T, Saul D, Van Snick J, Hermine O, Grassmann R (August 2001). "Autocrine antiapoptotic stimulation of cultured adult T-cell leukemia cells by overexpression of the chemokine I-309". Blood. 98 (4): 1150–9. doi: 10.1182/blood.v98.4.1150 . PMID   11493464.
  12. ↑ Bernardini G, Spinetti G, Ribatti D, Camarda G, Morbidelli L, Ziche M, et al. (December 2000). "I-309 binds to and activates endothelial cell functions and acts as an angiogenic molecule in vivo". Blood. 96 (13): 4039–45. doi:10.1182/blood.V96.13.4039. PMID   11110671.
  13. ↑ Takabatake N, Shibata Y, Abe S, Wada T, Machiya J, Igarashi A, et al. (October 2006). "A single nucleotide polymorphism in the CCL1 gene predicts acute exacerbations in chronic obstructive pulmonary disease". American Journal of Respiratory and Critical Care Medicine. 174 (8): 875–85. doi:10.1164/rccm.200603-443OC. PMID   16864713.
  14. ↑ Kielian T, Barry B, Hickey WF (April 2001). "CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses". Journal of Immunology. 166 (7): 4634–43. doi: 10.4049/jimmunol.166.7.4634 . PMID   11254722.
  15. ↑ Godiska R, Chantry D, Dietsch GN, Gray PW (May 1995). "Chemokine expression in murine experimental allergic encephalomyelitis". Journal of Neuroimmunology. 58 (2): 167–76. doi:10.1016/0165-5728(95)00008-p. PMID   7539012. S2CID   13148735.
  16. ↑ Horuk R, Hesselgesser J, Zhou Y, Faulds D, Halks-Miller M, Harvey S, et al. (January 1998). "The CC chemokine I-309 inhibits CCR8-dependent infection by diverse HIV-1 strains". The Journal of Biological Chemistry. 273 (1): 386–91. doi: 10.1074/jbc.273.1.386 . PMID   9417093.
  17. ↑ Denis C, Deiteren K, Mortier A, Tounsi A, Fransen E, Proost P, et al. (2012). "C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity". PLOS ONE. 7 (3): e34199. Bibcode:2012PLoSO...734199D. doi: 10.1371/journal.pone.0034199 . PMC   3313992 . PMID   22479563.
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