Chemokine (C-C motif) ligand 1 (CCL1) is also known assmall inducible cytokine A1 andI-309 in humans. CCL1 is a smallglycoprotein that belongs to theCC chemokine family.
CCL1 is encoded by CCL1gene which is one of the several chemokine genes clustered on thechromosome 17q11.2-q12 in humans.[1] It is expressed by specifically activatedT cells upon secondary stimulation.[2] The homologous mouse gene is termed Tca-3.
CCL1 stimulates a transient increase in the concentration of cytoplasmic freecalcium inmonocytes but not in other type of cells.[2] Furthermore, CCL1 inhibitsapoptosis in thymic cell lines by the RAS/MAPK pathway but can prevent dexamethasone-inducedapoptosis in cultured murine thymic lymphoma cells.[8][9][5]
CCL1 is involved in inflammatory processes throughleukocyte recruitment and could play a crucial role inangiogenesis and other viral and tumoral processes.[10][11][12] For example, CCL1 transcription was increased in primary humanCD4+ T cells expressing T cellimmunoglobulin and protein 3 containing the mucin domain (TIM-3) and was identified as a differentially transcribedgene 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 forin 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 CCL1gene 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 oflymphocytes andmonocytes 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] TheCCR8 receptor can serve as a basic receptor for various strains ofHIV-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]
^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.PMID11110671.
^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.PMID16864713.
