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Gene Review

CCL14  -  chemokine (C-C motif) ligand 14

Homo sapiens

Synonyms: C-C motif chemokine 14, CC-1, CC-3, CKB1, CKb1, ...
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Disease relevance of CCL14

  • A novel CC chemokine, HCC-1, was isolated from the hemofiltrate of patients with chronic renal failure [1].
  • To study HIV-1 escape from a coreceptor antagonist, the R5 primary isolate CC1/85 was passaged in peripheral blood mononuclear cells with increasing concentrations of the CCR5-specific small molecule inhibitor, AD101 [2].
  • An amino-terminally truncated p53 protein expressed in a human choriocarcinoma cell line, CC1 [3].
  • Alcaligenes sp. strain CC1 is able to grow on several alpha-chlorinated aliphatic acids (2-chlorobutyrate, 2-chloropropionate, and chloroacetate), as well as on the beta-chlorinated four-carbon aliphatic acids trans-3-chlorocrotonate, cis-3-chlorocrotonate, and 3-chlorobutyrate as sole carbon and energy sources [4].
  • The in vitro effects of orthosilicic acid (0-50 microM) on collagen type 1 synthesis was investigated using the human osteosarcoma cell line (MG-63), primary osteoblast-like cells derived from human bone marrow stromal cells, and an immortalized human early osteoblastic cell line (HCC1) [5].

High impact information on CCL14

  • Our results indicate that HCC-1 represents a nonfunctional precursor that can be rapidly converted to the active chemokine by proteolytic processing [6].
  • Using a cell line expressing CC chemokine receptor (CCR)5 as a bioassay, we isolated from human hemofiltrate an HCC-1 variant lacking the first eight amino acids [6].
  • Conditioned media from several tumor cell lines activated HCC-1 with a high efficiency, and this activity could be inhibited by serine protease inhibitors [6].
  • Unlike MIP-1 alpha and the other CC chemokines, HCC-1 is expressed constitutively in several normal tissues (spleen, liver, skeletal and heart muscle, gut, and bone marrow), and is present at high concentrations (1-80 nM) in plasma [1].
  • Mature HCC-1 has sequence identity of 46% with macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, and 29-37% with the other human CC chemokines [1].

Chemical compound and disease context of CCL14


Biological context of CCL14

  • At variance with the genes for HCC-1 and other human CC chemokines, which have a three-exon-two-intron structure, the HCC-2 gene consists of four exons and three introns [8].
  • Genetic sequence analysis combined with mutagenesis studies on clonal, chimeric viruses derived from CC1/85 and the PTCA variant showed that the most important changes were in the V1/V2 loop structure, one of them involving the loss of an N-linked glycosylation site [9].
  • In second-trimester fetal colonic mucosa, AH-6 bound to both proximal and distal segments whereas KH-1, CC-1, and CC-2 bound only to proximal segments [10].
  • The third hypothesis was that retinoic acid alters the cell cycle response of SiHa but not CC-1 to radiation [11].
  • The second hypothesis was that retinoic acid increases the proportion of G1-phase cells in SiHa but not in CC-1 [11].

Anatomical context of CCL14


Associations of CCL14 with chemical compounds

  • Each change individually caused partial resistance when they were introduced into the V3 loop of a CC1/85 clone, but their impact was dependent on the gp120 context in which they were made [13].
  • Glycosylated HCC-1 exhibits a molecular mass of 9621 Da due to O-glycosylation at position 7 (Ser-7) with two N-acetylneuraminic acids and the disaccharide N-acetylgalactosamine galactose [14].
  • Furthermore N-terminally truncated HCC-1 (3-74) and HCC-1 (4-74) were identified in the peptide library [14].
  • MATERIALS AND METHODS: Extracellular adenosine levels were analyzed by high-performance liquid chromatography in HCC1 and bone marrow stromal (BMS) cells [15].
  • One hypothesis was that SiHa is more sensitive to retinoic acid than CC-1 [11].

Other interactions of CCL14

  • Hemofiltrate CC chemokines with unique biochemical properties: HCC-1/CCL14a and HCC-2/CCL15 [16].
  • Studies performed with green fluorescent protein-tagged CCR5 confirmed that both HCC-1[9-74] and RANTES, but not full-length HCC-1, mediated specific internalization of the CCR5 HIV-1 entry cofactor [17].
  • Precursor plasma chemokines (CXCL7, CCL14) need to be proteolytically processed to obtain receptor affinity [18].
  • Pure preparations of uPA processed HCC-1 with high efficiency, without further degrading HCC-1[9-74] [19].

Analytical, diagnostic and therapeutic context of CCL14

  • Western blot analysis of human plasma extracts revealed a HCC-1 immunoreactive double band at 8-10 kDa indicating the presence of two distinct HCC-1 peptides [14].
  • Monomeric gp120 proteins expressed from CC1/85 and the PTCA variant did not differ in their affinities for sCD4, suggesting that the structural consequences of the sequence changes were manifested at the level of the native, trimeric Env complex [9].
  • Transcripts were not detected in the original HCC 1 and HCC2 upon Northern blot analysis [20].
  • DNA damage by asbestos was preceded by oxidant stress as shown by confocal scanning laser microscopy using MitoTracker Green FM and the oxidant probe Redox Sensor Red CC-1 [21].
  • Flow cytometry investigations with Red CC-1 showed an increase by more than 2 times suggesting a prooxidative role of bilirubin [22].


  1. HCC-1, a novel chemokine from human plasma. Schulz-Knappe, P., Mägert, H.J., Dewald, B., Meyer, M., Cetin, Y., Kubbies, M., Tomeczkowski, J., Kirchhoff, K., Raida, M., Adermann, K., Kist, A., Reinecke, M., Sillard, R., Pardigol, A., Uguccioni, M., Baggiolini, M., Forssmann, W.G. J. Exp. Med. (1996) [Pubmed]
  2. HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Trkola, A., Kuhmann, S.E., Strizki, J.M., Maxwell, E., Ketas, T., Morgan, T., Pugach, P., Xu, S., Wojcik, L., Tagat, J., Palani, A., Shapiro, S., Clader, J.W., McCombie, S., Reyes, G.R., Baroudy, B.M., Moore, J.P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. An amino-terminally truncated p53 protein expressed in a human choriocarcinoma cell line, CC1. Horikawa, I., Suzuki, M., Oshimura, M. Hum. Mol. Genet. (1995) [Pubmed]
  4. Microbial degradation of beta-chlorinated four-carbon aliphatic acids. Kohler-Staub, D., Kohler, H.P. J. Bacteriol. (1989) [Pubmed]
  5. Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro. Reffitt, D.M., Ogston, N., Jugdaohsingh, R., Cheung, H.F., Evans, B.A., Thompson, R.P., Powell, J.J., Hampson, G.N. Bone (2003) [Pubmed]
  6. Natural proteolytic processing of hemofiltrate CC chemokine 1 generates a potent CC chemokine receptor (CCR)1 and CCR5 agonist with anti-HIV properties. Detheux, M., Ständker, L., Vakili, J., Münch, J., Forssmann, U., Adermann, K., Pöhlmann, S., Vassart, G., Kirchhoff, F., Parmentier, M., Forssmann, W.G. J. Exp. Med. (2000) [Pubmed]
  7. Immunohistochemical analysis of proliferation and differentiation in organotypic cultures of cervical tumor cell lines. Benbrook, D.M., Rogers, R.S., Medlin, M.A., Dunn, S.T. Tissue & cell. (1995) [Pubmed]
  8. HCC-2, a human chemokine: gene structure, expression pattern, and biological activity. Pardigol, A., Forssmann, U., Zucht, H.D., Loetscher, P., Schulz-Knappe, P., Baggiolini, M., Forssmann, W.G., Mägert, H.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. The prolonged culture of human immunodeficiency virus type 1 in primary lymphocytes increases its sensitivity to neutralization by soluble CD4. Pugach, P., Kuhmann, S.E., Taylor, J., Marozsan, A.J., Snyder, A., Ketas, T., Wolinsky, S.M., Korber, B.T., Moore, J.P. Virology (2004) [Pubmed]
  10. Expression of LeY and extended LeY blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues. Kim, Y.S., Yuan, M., Itzkowitz, S.H., Sun, Q.B., Kaizu, T., Palekar, A., Trump, B.F., Hakomori, S. Cancer Res. (1986) [Pubmed]
  11. Differential retinoic acid radiosensitization of cervical carcinoma cell lines. Benbrook, D.M., Shen-Gunther, J., Nuñez, E.R., Dynlacht, J.R. Clin. Cancer Res. (1997) [Pubmed]
  12. Morphological and physiological comparisons of two types of allatostatin in the brain and retrocerebral complex of the tomato moth, Lacanobia oleracea (Lepidoptera: Noctuidae). Audsley, N., Duve, H., Thorpe, A., Weaver, R.J. J. Comp. Neurol. (2000) [Pubmed]
  13. Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor. Kuhmann, S.E., Pugach, P., Kunstman, K.J., Taylor, J., Stanfield, R.L., Snyder, A., Strizki, J.M., Riley, J., Baroudy, B.M., Wilson, I.A., Korber, B.T., Wolinsky, S.M., Moore, J.P. J. Virol. (2004) [Pubmed]
  14. Posttranslationally processed forms of the human chemokine HCC-1. Richter, R., Schulz-Knappe, P., John, H., Forssmann, W.G. Biochemistry (2000) [Pubmed]
  15. Human osteoblast precursors produce extracellular adenosine, which modulates their secretion of IL-6 and osteoprotegerin. Evans, B.A., Elford, C., Pexa, A., Francis, K., Hughes, A.C., Deussen, A., Ham, J. J. Bone Miner. Res. (2006) [Pubmed]
  16. Hemofiltrate CC chemokines with unique biochemical properties: HCC-1/CCL14a and HCC-2/CCL15. Forssmann, U., Mägert, H.J., Adermann, K., Escher, S.E., Forssmann, W.G. J. Leukoc. Biol. (2001) [Pubmed]
  17. Hemofiltrate CC chemokine 1[9-74] causes effective internalization of CCR5 and is a potent inhibitor of R5-tropic human immunodeficiency virus type 1 strains in primary T cells and macrophages. Münch, J., Ständker, L., Pöhlmann, S., Baribaud, F., Papkalla, A., Rosorius, O., Stauber, R., Sass, G., Heveker, N., Adermann, K., Escher, S., Klüver, E., Doms, R.W., Forssmann, W.G., Kirchhoff, F. Antimicrob. Agents Chemother. (2002) [Pubmed]
  18. Chemokine-protease interactions in cancer. Van Damme, J., Struyf, S., Opdenakker, G. Semin. Cancer Biol. (2004) [Pubmed]
  19. Urokinase plasminogen activator and plasmin efficiently convert hemofiltrate CC chemokine 1 into its active. Vakili, J., Ständker, L., Detheux, M., Vassart, G., Forssmann, W.G., Parmentier, M. J. Immunol. (2001) [Pubmed]
  20. Identification of transforming genes as hst in DNA samples from two human hepatocellular carcinomas. Nakagama, H., Ohnishi, S., Imawari, M., Hirai, H., Takaku, F., Sakamoto, H., Terada, M., Nagao, M., Sugimura, T. Jpn. J. Cancer Res. (1987) [Pubmed]
  21. Asbestos induces mitochondrial DNA damage and dysfunction linked to the development of apoptosis. Shukla, A., Jung, M., Stern, M., Fukagawa, N.K., Taatjes, D.J., Sawyer, D., Van Houten, B., Mossman, B.T. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  22. Bilirubin exhibits a novel anti-cancer effect on human adenocarcinoma. Rao, P., Suzuki, R., Mizobuchi, S., Yamaguchi, T., Sasaguri, S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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