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Gene Review

CCL15  -  chemokine (C-C motif) ligand 15

Homo sapiens

Synonyms: C-C motif chemokine 15, Chemokine CC-2, HCC-2, HMRP-2B, LKN-1, ...
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Disease relevance of CCL15


High impact information on CCL15

  • Desensitization studies indicate that HCC-2 acts mainly via CC chemokine receptor CCR1 [6].
  • HCC-2, a human chemokine: gene structure, expression pattern, and biological activity [6].
  • In contrast to HCC-1, which is expressed constitutively in numerous human tissues, HCC-2 is expressed only in the gut and the liver [6].
  • Highly purified recombinant HCC-2 was tested on neutrophils, eosinophils, monocytes, and lymphocytes and was found to exhibit marked functional similarities to macrophage inflammatory protein 1alpha [6].
  • 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 [6].

Biological context of CCL15

  • Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells [2].
  • In consensus with observations in the first scan, the present study identified haplotypes within CCL3 and CCL15 in the telomeric CCL cluster [7].
  • When the nucleotide sequences of the MPIF-1 and HCC-2 genes are compared, they are well conserved, including introns and flanking sequences, except for the middle region of the long first intron, indicating that they have been generated recently in evolutionary terms by duplication [8].
  • In contrast to most other human CC chemokine genes that consist of three exons, the MPIF-1 and HCC-2 genes, separated by 12 kb, have four exons [8].
  • Involvement of two NF-kappaB binding sites in PMA-induced expression of the human leukotactin-1/CCL15 gene in U937 monocytoid cells [9].

Anatomical context of CCL15


Associations of CCL15 with chemical compounds

  • Further we demonstrate that the third disulfide bond of CCL15 and an exchange of tyrosine in position 70 by a leucine residue, which is conserved in CXC chemokines, do not alter the interaction with CCR1 [13].
  • Chemotactic activity of Lkn-1 was inhibited by the treatment of cycloheximide and actinomycin D suggesting that newly synthesized proteins are needed for chemotaxis [2].
  • Deletion of 29 amino acids, however, abolished the agonistic activity almost completely showing that at least 3 amino acid residues preceding the first cysteine at the NH(2) terminus are essential for the biological activity of Lkn-1 [14].
  • Serial deletion studies showed that at least three amino acid residues, alanine-alanine-aspartic acid (A-A-D), preceding the first cysteine at the NH(2)-terminus are essential for the biological activity of Lkn-1 [15].
  • Protein kinase C delta (PKC delta) specific inhibitor rottlerin inhibited ERK activation in Lkn-1-stimulated cells [4].

Physical interactions of CCL15

  • These data indicate that LZIP binds to CCR1 and that the interaction between CCR1 and LZIP participates in regulation of Lkn-1-dependent cell migration without affecting the chemotactic activities of other CC chemokines that bind to CCR1 [16].

Regulatory relationships of CCL15

  • Our findings indicate that transcription of the CCL15 gene is regulated by AP-1 and NF-kappaB through MEK and JNK MAPK pathways in monocytoid cells [17].

Other interactions of CCL15

  • Hemofiltrate CC chemokines with unique biochemical properties: HCC-1/CCL14a and HCC-2/CCL15 [18].
  • In contrast, a CCL15 derivative lacking the carboxy-terminal alpha-helix exhibits a complete loss of tertiary structure and hence loss of CCR1 agonistic and binding activity [13].
  • The present study replicates our previous findings and further suggests the existence of MS associated haplotypes within genes of CCL3 and CCL15 [7].
  • We show here that neutrophils may support this process by activation of CCL15, a human chemokine circulating in blood plasma [1].
  • Neutrophil cathepsin G was identified as the principal protease to produce delta23 and delta26 CCL15 [1].

Analytical, diagnostic and therapeutic context of CCL15


  1. Quantum proteolytic activation of chemokine CCL15 by neutrophil granulocytes modulates mononuclear cell adhesiveness. Richter, R., Bistrian, R., Escher, S., Forssmann, W.G., Vakili, J., Henschler, R., Spodsberg, N., Frimpong-Boateng, A., Forssmann, U. J. Immunol. (2005) [Pubmed]
  2. Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells. Ko, J., Kim, I.S., Jang, S.W., Lee, Y.H., Shin, S.Y., Min, d.o. .S., Na, D.S. FEBS Lett. (2002) [Pubmed]
  3. Tumor progression despite massive influx of activated CD8(+) T cells in a patient with malignant melanoma ascites. Harlin, H., Kuna, T.V., Peterson, A.C., Meng, Y., Gajewski, T.F. Cancer Immunol. Immunother. (2006) [Pubmed]
  4. Leukotactin-1-induced ERK activation is mediated via Gi/Go protein/PLC/PKC delta/Ras cascades in HOS cells. Kim, I.S., Ryang, Y.S., Kim, Y.S., Jang, S.W., Sung, H.J., Lee, Y.H., Kim, J., Na, D.S., Ko, J. Life Sci. (2003) [Pubmed]
  5. A novel chemokine, Leukotactin-1, induces chemotaxis, pro-atherogenic cytokines, and tissue factor expression in atherosclerosis. Lee, W.H., Kim, S.H., Jeong, E.M., Choi, Y.H., Kim, D.I., Lee, B.B., Cho, Y.S., Kwon, B.S., Park, J.E. Atherosclerosis (2002) [Pubmed]
  6. 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]
  7. Haplotypes within genes of beta-chemokines in 17q11 are associated with multiple sclerosis: a second phase study. Vyshkina, T., Kalman, B. Hum. Genet. (2005) [Pubmed]
  8. Organization of the chemokine gene cluster on human chromosome 17q11.2 containing the genes for CC chemokine MPIF-1, HCC-2, HCC-1, LEC, and RANTES. Nomiyama, H., Fukuda, S., Iio, M., Tanase, S., Miura, R., Yoshie, O. J. Interferon Cytokine Res. (1999) [Pubmed]
  9. Involvement of two NF-kappaB binding sites in PMA-induced expression of the human leukotactin-1/CCL15 gene in U937 monocytoid cells. Shin, Y.H., Shim, J.J., Hur, M.W., Kang, C.J., Kim, J. Mol. Cells (2004) [Pubmed]
  10. Macrophage inflammatory protein-1. Maurer, M., von Stebut, E. Int. J. Biochem. Cell Biol. (2004) [Pubmed]
  11. Angiogenic activity of human CC chemokine CCL15 in vitro and in vivo. Hwang, J., Kim, C.W., Son, K.N., Han, K.Y., Lee, K.H., Kleinman, H.K., Ko, J., Na, D.S., Kwon, B.S., Gho, Y.S., Kim, J. FEBS Lett. (2004) [Pubmed]
  12. Characterisation of macrophage inflammatory protein-5/human CC cytokine-2, a member of the macrophage-inflammatory-protein family of chemokines. Coulin, F., Power, C.A., Alouani, S., Peitsch, M.C., Schroeder, J.M., Moshizuki, M., Clark-Lewis, I., Wells, T.N. Eur. J. Biochem. (1997) [Pubmed]
  13. Functional analysis of chemically synthesized derivatives of the human CC chemokine CCL15/HCC-2, a high affinity CCR1 ligand. Escher, S.E., Forssmann, U., Frimpong-Boateng, A., Adermann, K., Vakili, J., Sticht, H., Detheux, M. J. Pept. Res. (2004) [Pubmed]
  14. Truncation of NH2-terminal amino acid residues increases agonistic potency of leukotactin-1 on CC chemokine receptors 1 and 3. Lee, J.K., Lee, E.H., Yun, Y.P., Kim, K., Kwack, K., Na, D.S., Kwon, B.S., Lee, C.K. J. Biol. Chem. (2002) [Pubmed]
  15. Identification of NH(2)-terminal amino acid residues essential for the biological activity of leukotactin-1. Lee, J.K., Kim, H.S., Im, S.A., Kim, K., Kwon, B.S., Lee, C.K. Immunol. Lett. (2005) [Pubmed]
  16. Human LZIP binds to CCR1 and differentially affects the chemotactic activities of CCR1-dependent chemokines. Ko, J., Jang, S.W., Kim, Y.S., Kim, I.S., Sung, H.J., Kim, H.H., Park, J.Y., Lee, Y.H., Kim, J., Na, D.S. FASEB J. (2004) [Pubmed]
  17. Transcriptional regulation of human CC chemokine CCL15 gene by NF-kappaB and AP-1 elements in PMA-stimulated U937 monocytoid cells. Shin, Y.H., Son, K.N., Lee, G.W., Kwon, B.S., Kim, J. Biochim. Biophys. Acta (2005) [Pubmed]
  18. 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]
  19. 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]
  20. Involvement of leukotactin-1, a novel CC chemokine, in human atherosclerosis. Yu, R., Kim, C.S., Kawada, T., Kwon, T.W., Lim, T.H., Kim, Y.W., Kwon, B.S. Atherosclerosis (2004) [Pubmed]
  21. Extent of resection for hepatocellular carcinoma 2 cm or less in greatest diameter. Yamamoto, M., Takasaki, K., Otsubo, T., Saito, A., Nakano, M. Am. J. Surg. (2002) [Pubmed]
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