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Gene Review

CCL1  -  chemokine (C-C motif) ligand 1

Homo sapiens

Synonyms: C-C motif chemokine 1, I-309, P500, SCYA1, SISe, ...
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Disease relevance of CCL1


Psychiatry related information on CCL1

  • Conclusions: Variants in the CCL1 gene are associated with susceptibility to AEs through their potential implication in the host defense mechanisms against AEs [4].

High impact information on CCL1

  • Importantly, CCL1 is constitutively expressed at strategic cutaneous locations, including dermal microvessels and epidermal antigen-presenting cells [6].
  • Here, we show that the majority of human T cells in healthy skin express the chemokine receptor CCR8 and respond to its selective ligand I-309/CCL1 [6].
  • They prevalently localized to perivascular areas of fibrous septa and responded to the chemoattractant activity of CCL1/I-309, which was found to be produced by either thymic medullary macrophages or fibrous septa epithelial cells [7].
  • Blood-borne CD4(+) T cells that migrate in response to CCL1 and CCL22 exhibit a reduced alloproliferative response, dependent on the increased frequency of Treg cells in the migrated population [8].
  • The human CC chemokine I-309 is a potent monocyte chemoattractant and inhibits apoptosis in thymic cell lines [9].

Chemical compound and disease context of CCL1


Biological context of CCL1

  • I-309 and CCR8 mRNAs were not detected in unaffected skin and were up-regulated at the skin site of nickel-allergic reaction, with an earlier expression kinetics compared with IL-10 and IL-4 [12].
  • BAL fluids were analyzed for total cell counts and differentials, and supernatants were assayed by ELISA for levels of TARC, MDC, and I-309 [13].
  • Inhibition of this calcium increase, using the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester or the calcium store-operated channel inhibitor 2-aminoethoxydiphenyl borate, fully blocked CCL1 up-regulation [14].
  • The CC chemokine I-309 was the only agonist that selectively induced intracellular Ca2+ mobilization and chemotaxis in receptor-transfected 300-19 cells [15].
  • The molar concentration of LEC required to induce maximum cell migration is 20- to 200-fold greater than that required for RANTES or I309, respectively [16].

Anatomical context of CCL1


Associations of CCL1 with chemical compounds

  • Moreover, 2,3,7,8-tetrachlorodibenzo-p-dioxin triggered AhR binding to this CCL1 promoter element as revealed by chromatin immunoprecipitation experiments and electrophoretic mobility shift assays [14].
  • The three-dimensional solution structure of I-309 was determined by (1)H nuclear magnetic resonance spectroscopy and dynamic simulated annealing [19].
  • It was insensitive to eotaxin, vMIP-1 and I309 when tested individually, but was inhibited completely when vMIP-1 or I309 was combined with AMD3100 [20].
  • NH(2)-terminal extension of the mature CCL1 sequence by a serine residue (Ser-CCL1) resulted in a partial agonist with a reduced affinity for CCR8, suggesting that the NH(2) terminus of the ligand plays a role in ligand binding to an intrahelical site [21].
  • In addition, it was observed that CB-derived MCs uniquely release histamine and CCL1, which are produced by human MCs but not by human monocytes, in response to peptidoglycan (PGN), although it had been controversy issue whether CB-derived MCs could, in fact, induce degranulation in response to PGN [22].

Physical interactions of CCL1

  • Both I309 and vMIP-1 bind CCR8, strongly suggesting that this isolate can use CCR8 on primary cells [20].

Regulatory relationships of CCL1

  • CCL7 was found to inhibit both Ser-CCL1 and vMIP-I responses but not those of CCL1 itself [21].
  • I-309 antisense oligonucleotides also inhibited the induction of endothelial monocyte chemotactic activity by apo(a) [23].

Other interactions of CCL1

  • Viral macrophage inflammatory protein (vMIP)-I, I-309, and TARC competed with the binding of (125)I-309 to AD cells with varying affinities [24].
  • Results indicate that skin-homing regulatory Th(IL-10) lymphocytes coexpress functional Th1- and Th2-associated chemokine receptors, and that CCR8/I-309-driven recruitment of both resting and activated Th(IL-10) cells may be critically involved in the regulation of Th1-mediated skin allergic disorders [12].
  • This binding seems species-specific as 7L does not bind the murine orthologues of CCL1 and CCL7 in the assays used [25].
  • Transcripts for the chemokines MIP-1alpha, MIP-1beta, I-309, or lymphotactin could not be detected [26].
  • Thus, CCL1 is a CC chemokine with a unique pattern of regulation associated with a distinct form of M2 (Type 2, M2b) monocyte activation, which participates in macrophage-dependent regulatory circuits of innate and adaptive immunity [1].

Analytical, diagnostic and therapeutic context of CCL1


  1. Differential regulation of chemokine production by Fcgamma receptor engagement in human monocytes: association of CCL1 with a distinct form of M2 monocyte activation (M2b, Type 2). Sironi, M., Martinez, F.O., D'Ambrosio, D., Gattorno, M., Polentarutti, N., Locati, M., Gregorio, A., Iellem, A., Cassatella, M.A., Van Damme, J., Sozzani, S., Martini, A., Sinigaglia, F., Vecchi, A., Mantovani, A. J. Leukoc. Biol. (2006) [Pubmed]
  2. CCL1-CCR8 interactions: an axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation. Gombert, M., Dieu-Nosjean, M.C., Winterberg, F., Bünemann, E., Kubitza, R.C., Da Cunha, L., Haahtela, A., Lehtimäki, S., Müller, A., Rieker, J., Meller, S., Pivarcsi, A., Koreck, A., Fridman, W.H., Zentgraf, H.W., Pavenstädt, H., Amara, A., Caux, C., Kemeny, L., Alenius, H., Lauerma, A., Ruzicka, T., Zlotnik, A., Homey, B. J. Immunol. (2005) [Pubmed]
  3. Crystal structure of viral macrophage inflammatory protein I encoded by Kaposi's sarcoma-associated herpesvirus at 1.7A. Luz, J.G., Yu, M., Su, Y., Wu, Z., Zhou, Z., Sun, R., Wilson, I.A. J. Mol. Biol. (2005) [Pubmed]
  4. A Single Nucleotide Polymorphism in the CCL1 Gene Predicts Acute Exacerbations in Chronic Obstructive Pulmonary Disease. Takabatake, N., Shibata, Y., Abe, S., Wada, T., Machiya, J., Igarashi, A., Tokairin, Y., Ji, G., Sato, H., Sata, M., Takeishi, Y., Emi, M., Muramatsu, M., Kubota, I. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  5. Design, Synthesis, and Progress toward Optimization of Potent Small Molecule Antagonists of CC Chemokine Receptor 8 (CCR8). Ghosh, S., Elder, A., Guo, J., Mani, U., Patane, M., Carson, K., Ye, Q., Bennett, R., Chi, S., Jenkins, T., Guan, B., Kolbeck, R., Smith, S., Zhang, C., Larosa, G., Jaffee, B., Yang, H., Eddy, P., Lu, C., Uttamsingh, V., Horlick, R., Harriman, G., Flynn, D. J. Med. Chem. (2006) [Pubmed]
  6. A skin-selective homing mechanism for human immune surveillance T cells. Schaerli, P., Ebert, L., Willimann, K., Blaser, A., Roos, R.S., Loetscher, P., Moser, B. J. Exp. Med. (2004) [Pubmed]
  7. Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes. Annunziato, F., Cosmi, L., Liotta, F., Lazzeri, E., Manetti, R., Vanini, V., Romagnani, P., Maggi, E., Romagnani, S. J. Exp. Med. (2002) [Pubmed]
  8. Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells. Iellem, A., Mariani, M., Lang, R., Recalde, H., Panina-Bordignon, P., Sinigaglia, F., D'Ambrosio, D. J. Exp. Med. (2001) [Pubmed]
  9. Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309. Tiffany, H.L., Lautens, L.L., Gao, J.L., Pease, J., Locati, M., Combadiere, C., Modi, W., Bonner, T.I., Murphy, P.M. J. Exp. Med. (1997) [Pubmed]
  10. Dopamine D2L receptor couples to G alpha i2 and G alpha i3 but not G alpha i1, leading to the inhibition of adenylate cyclase in transfected cell lines. O'Hara, C.M., Tang, L., Taussig, R., Todd, R.D., O'Malley, K.L. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  11. CCR8 on human thymocytes functions as a human immunodeficiency virus type 1 coreceptor. Lee, S., Tiffany, H.L., King, L., Murphy, P.M., Golding, H., Zaitseva, M.B. J. Virol. (2000) [Pubmed]
  12. Chemokine receptor expression and function in CD4+ T lymphocytes with regulatory activity. Sebastiani, S., Allavena, P., Albanesi, C., Nasorri, F., Bianchi, G., Traidl, C., Sozzani, S., Girolomoni, G., Cavani, A. J. Immunol. (2001) [Pubmed]
  13. Release of both CCR4-active and CXCR3-active chemokines during human allergic pulmonary late-phase reactions. Bochner, B.S., Hudson, S.A., Xiao, H.Q., Liu, M.C. J. Allergy Clin. Immunol. (2003) [Pubmed]
  14. Aryl hydrocarbon receptor- and calcium-dependent induction of the chemokine CCL1 by the environmental contaminant benzo[a]pyrene. N'Diaye, M., Le Ferrec, E., Lagadic-Gossmann, D., Corre, S., Gilot, D., Lecureur, V., Monteiro, P., Rauch, C., Galibert, M.D., Fardel, O. J. Biol. Chem. (2006) [Pubmed]
  15. Identification of CCR8, the receptor for the human CC chemokine I-309. Roos, R.S., Loetscher, M., Legler, D.F., Clark-Lewis, I., Baggiolini, M., Moser, B. J. Biol. Chem. (1997) [Pubmed]
  16. LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8. Howard, O.M., Dong, H.F., Shirakawa, A.K., Oppenheim, J.J. Blood (2000) [Pubmed]
  17. Modulation of chemokine receptor expression and chemotactic responsiveness during differentiation of human naive T cells into Th1 or Th2 cells. Colantonio, L., Recalde, H., Sinigaglia, F., D'Ambrosio, D. Eur. J. Immunol. (2002) [Pubmed]
  18. Chemokine receptor-8: potential role in atherogenesis. Harpel, P.C., Haque, N.S. Isr. Med. Assoc. J. (2002) [Pubmed]
  19. Human CC chemokine I-309, structural consequences of the additional disulfide bond. Keizer, D.W., Crump, M.P., Lee, T.W., Slupsky, C.M., Clark-Lewis, I., Sykes, B.D. Biochemistry (2000) [Pubmed]
  20. Use of alternate coreceptors on primary cells by two HIV-1 isolates. Cilliers, T., Willey, S., Sullivan, W.M., Patience, T., Pugach, P., Coetzer, M., Papathanasopoulos, M., Moore, J.P., Trkola, A., Clapham, P., Morris, L. Virology (2005) [Pubmed]
  21. Structure/Function Relationships of CCR8 Agonists and Antagonists: AMINO-TERMINAL EXTENSION OF CCL1 BY A SINGLE AMINO ACID GENERATES A PARTIAL AGONIST. Fox, J.M., Najarro, P., Smith, G.L., Struyf, S., Proost, P., Pease, J.E. J. Biol. Chem. (2006) [Pubmed]
  22. Differential gene expression profile between cord blood progenitor-derived and adult progenitor-derived human mast cells. Inomata, N., Tomita, H., Ikezawa, Z., Saito, H. Immunol. Lett. (2005) [Pubmed]
  23. CC chemokine I-309 is the principal monocyte chemoattractant induced by apolipoprotein(a) in human vascular endothelial cells. Haque, N.S., Zhang, X., French, D.L., Li, J., Poon, M., Fallon, J.T., Gabel, B.R., Taubman, M.B., Koschinsky, M., Harpel, P.C. Circulation (2000) [Pubmed]
  24. Expression and regulation of chemokine receptors in human natural killer cells. Inngjerdingen, M., Damaj, B., Maghazachi, A.A. Blood (2001) [Pubmed]
  25. Yaba-like disease virus protein 7L is a cell-surface receptor for chemokine CCL1. Najarro, P., Lee, H.J., Fox, J., Pease, J., Smith, G.L. J. Gen. Virol. (2003) [Pubmed]
  26. Chemokine and chemokine receptor expression in a novel human mesangial cell line. Banas, B., Luckow, B., Möller, M., Klier, C., Nelson, P.J., Schadde, E., Brigl, M., Halevy, D., Holthöfer, H., Reinhart, B., Schlöndorff, D. J. Am. Soc. Nephrol. (1999) [Pubmed]
  27. The chemokine binding protein m3 prevents diabetes induced by multiple low doses of streptozotocin. Martin, A.P., Alexander-Brett, J.M., Canasto-Chibuque, C., Garin, A., Bromberg, J.S., Fremont, D.H., Lira, S.A. J. Immunol. (2007) [Pubmed]
  28. Autocrine antiapoptotic stimulation of cultured adult T-cell leukemia cells by overexpression of the chemokine I-309. Ruckes, T., Saul, D., Van Snick, J., Hermine, O., Grassmann, R. Blood (2001) [Pubmed]
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