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Gene Review

Ccl6  -  chemokine (C-C motif) ligand 6

Mus musculus

Synonyms: C-C motif chemokine 6, C10, MRP-1, Protein C10, Scya6, ...
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Disease relevance of Ccl6

  • Immunoneutralization of peritoneal C10 levels with polyclonal anti-C10 antiserum during CLP-induced peritonitis negatively impacted mouse survival over 4 days [1].
  • The lack of bacteremia in C10-treated mice appeared to be related, in part, to in vitro evidence that C10 significantly enhanced the bacterial phagocytic activity of peritoneal macrophages [1].
  • Immunomodulatory role of C10 chemokine in a murine model of allergic bronchopulmonary aspergillosis [2].
  • Hyperthermic stress (43 degrees C, 180 min), which induces reactivation of latent HSV-1 from TG cell cultures, significantly reduced IL-6 and C-10 levels from both uninfected and latently infected TG cell cultures [3].
  • To explore the protective function of the mouse mrp1 protein during drug treatment, we investigated the toxicity caused by the anticancer drug etoposide-phosphate (ETOPOPHOS) in mice lacking the mrp1 gene (mrp1(-/-) mice) [4].

High impact information on Ccl6

  • At the mechanistic level, bacterial levels in Stat6-/- mice were much lower than in WT mice, which was associated with increased peritoneal levels of interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, macrophage-derived chemokine (MDC), and C10, known to enhance bacterial clearance [5].
  • We show here that the lack of mrp1 protein results in increased etoposide-induced damage to the mucosa of the oropharyngeal cavity and to the seminiferous tubules of the testis [4].
  • Our results indicate that specific inhibitors of MRP1 used to reverse MDR, in combination with carcinostatic drugs transported by MRP1, might lead to drug-induced mucositis, (temporary) infertility, and diabetes insipidus [4].
  • We also find drug-induced polyuria in mrp1(-/-) mice, which correlates with the presence of mrp1 protein in the urinary collecting tubules, the major site of kidney water reabsorption [4].
  • The high concentrations of mrp1 that we find in the basal layers of the oropharyngeal mucosa and in the basal membrane of the Sertoli cells in the testis apparently protect wild-type mice against this tissue damage [4].

Chemical compound and disease context of Ccl6


Biological context of Ccl6


Anatomical context of Ccl6


Associations of Ccl6 with chemical compounds

  • Macrophage inflammatory protein related protein-2 (mMRP-2) and Mu C10 (mMRP-1), which are murine C6 beta-chemokines, also inhibited colony formation by CB CD34+ cells [19].
  • Thus, although the C10 gene contains a novel exon not found in any other members of the chemokine superfamily, its chromosomal location and conservation of cysteine residues and other structural features suggest that it evolved from the same ancestral gene as other members of the beta-chemokine family [12].
  • By contrast, annexin 1 secretion is not blocked by other inhibitors of MRP1 (indomethacin, MK571), MRP2 (ochratoxin A1 or MK571), MRP5 (trequinsin or sulfinpyrazone) or by verapamil, cyclosporin A or glyburide [20].
  • Most importantly, when EL4 cells were incubated in the presence of the MRP1 inhibitors indomethacin and MK 571 for 6 days, they started to express CD4 and CD8 molecules on their surface, producing double-positive cells and CD8 single-positive cells [21].
  • In the harvested cells the transcripts for mdr1a and mrp1, but not those for mdr1b, mrp2 and CYP3A, were detected, and treatment with verapamil or rifampicin did not modify the levels of the transcripts [22].

Regulatory relationships of Ccl6

  • Additionally, in C10 cells expressing a mutant form of TNF-R1, H2O2-induced JNK activation was also inhibited [23].

Other interactions of Ccl6


Analytical, diagnostic and therapeutic context of Ccl6


  1. Chemokine C10 promotes disease resolution and survival in an experimental model of bacterial sepsis. Steinhauser, M.L., Hogaboam, C.M., Matsukawa, A., Lukacs, N.W., Strieter, R.M., Kunkel, S.L. Infect. Immun. (2000) [Pubmed]
  2. Immunomodulatory role of C10 chemokine in a murine model of allergic bronchopulmonary aspergillosis. Hogaboam, C.M., Gallinat, C.S., Taub, D.D., Strieter, R.M., Kunkel, S.L., Lukacs, N.W. J. Immunol. (1999) [Pubmed]
  3. Cytokine and chemokine production in HSV-1 latently infected trigeminal ganglion cell cultures: effects of hyperthermic stress. Carr, D.J., Noisakran, S., Halford, W.P., Lukacs, N., Asensio, V., Campbell, I.L. J. Neuroimmunol. (1998) [Pubmed]
  4. Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage. Wijnholds, J., Scheffer, G.L., van der Valk, M., van der Valk, P., Beijnen, J.H., Scheper, R.J., Borst, P. J. Exp. Med. (1998) [Pubmed]
  5. Pivotal role of signal transducer and activator of transcription (Stat)4 and Stat6 in the innate immune response during sepsis. Matsukawa, A., Kaplan, M.H., Hogaboam, C.M., Lukacs, N.W., Kunkel, S.L. J. Exp. Med. (2001) [Pubmed]
  6. A Trypanosoma cruzi membrane protein shares an epitope with a lymphocyte activation antigen and induces crossreactive antibodies. Hernández-Munaín, C., De Diego, J.L., Alcina, A., Fresno, M. J. Exp. Med. (1992) [Pubmed]
  7. Bilirubin protects astrocytes from its own toxicity by inducing up-regulation and translocation of multidrug resistance-associated protein 1 (Mrp1). Gennuso, F., Fernetti, C., Tirolo, C., Testa, N., L'Episcopo, F., Caniglia, S., Morale, M.C., Ostrow, J.D., Pascolo, L., Tiribelli, C., Marchetti, B. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Xie, T.X., Wei, D., Liu, M., Gao, A.C., Ali-Osman, F., Sawaya, R., Huang, S. Oncogene (2004) [Pubmed]
  9. Structure-activity study of inhibition of amphotericin B (Fungizone) binding to sterols, toxicity to cells, and lethality to mice by esters of sucrose. Gruda, I., Milette, D., Brother, M., Kobayashi, G.S., Medoff, G., Brajtburg, J. Antimicrob. Agents Chemother. (1991) [Pubmed]
  10. Modulation of Schistosoma japonicum pulmonary egg granulomas with monoclonal antibodies. Sidner, R.A., Carter, C.E., Colley, D.G. Am. J. Trop. Med. Hyg. (1987) [Pubmed]
  11. Persistent over-expression of specific CC class chemokines correlates with macrophage and T-cell recruitment in mdx skeletal muscle. Porter, J.D., Guo, W., Merriam, A.P., Khanna, S., Cheng, G., Zhou, X., Andrade, F.H., Richmonds, C., Kaminski, H.J. Neuromuscul. Disord. (2003) [Pubmed]
  12. The gene for C10, a member of the beta-chemokine family, is located on mouse chromosome 11 and contains a novel second exon not found in other chemokines. Berger, M.S., Kozak, C.A., Gabriel, A., Prystowsky, M.B. DNA Cell Biol. (1993) [Pubmed]
  13. Silica-induced activation of c-Jun-NH2-terminal amino kinases, protracted expression of the activator protein-1 proto-oncogene, fra-1, and S-phase alterations are mediated via oxidative stress. Shukla, A., Timblin, C.R., Hubbard, A.K., Bravman, J., Mossman, B.T. Cancer Res. (2001) [Pubmed]
  14. Differing specificities for 4-aminofolate analogues of folylpolyglutamyl synthetase from tumors and proliferative intestinal epithelium of the mouse with significance for selective antitumor action. Rumberger, B.G., Barrueco, J.R., Sirotnak, F.M. Cancer Res. (1990) [Pubmed]
  15. Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis. Belperio, J.A., Dy, M., Burdick, M.D., Xue, Y.Y., Li, K., Elias, J.A., Keane, M.P. Am. J. Respir. Cell Mol. Biol. (2002) [Pubmed]
  16. Functional expression of CCL6 by rat microglia: a possible role of CCL6 in cell-cell communication. Kanno, M., Suzuki, S., Fujiwara, T., Yokoyama, A., Sakamoto, A., Takahashi, H., Imai, Y., Tanaka, J. J. Neuroimmunol. (2005) [Pubmed]
  17. Divergent regulation of the murine CC chemokine C10 by Th(1) and Th(2) cytokines. Orlofsky, A., Wu, Y., Prystowsky, M.B. Cytokine (2000) [Pubmed]
  18. The healing skin wound: a novel site of action of the chemokine C10. Kaesler, S., Regenbogen, J., Durka, S., Goppelt, A., Werner, S. Cytokine (2002) [Pubmed]
  19. Differentiation of CD34+ cells from human cord blood and murine bone marrow is suppressed by C6 beta-chemokines. Han, I.S., Ra, J.S., Kim, M.W., Lee, E.A., Jun, H.Y., Park, S.K., Kwon, B.S. Mol. Cells (2003) [Pubmed]
  20. Mediation of annexin 1 secretion by a probenecid-sensitive ABC-transporter in rat inflamed mucosa. Wein, S., Fauroux, M., Laffitte, J., de Nadaï, P., Guaïni, C., Pons, F., Coméra, C. Biochem. Pharmacol. (2004) [Pubmed]
  21. Expression and activity of multidrug resistance protein 1 in a murine thymoma cell line. Echevarria-Lima, J., Kyle-Cezar, F., P Leite, D.F., Capella, L., Capella, M.A., Rumjanek, V.M. Immunology (2005) [Pubmed]
  22. Rifampicin and verapamil induce the expression of P-glycoprotein in vivo in Ehrlich ascites tumor cells. Granzotto, M., Drigo, I., Candussio, L., Rosati, A., Bartoli, F., Giraldi, T., Decorti, G. Cancer Lett. (2004) [Pubmed]
  23. Hydrogen peroxide signaling through tumor necrosis factor receptor 1 leads to selective activation of c-Jun N-terminal kinase. Pantano, C., Shrivastava, P., McElhinney, B., Janssen-Heininger, Y. J. Biol. Chem. (2003) [Pubmed]
  24. Chemokine expression in murine experimental allergic encephalomyelitis. Godiska, R., Chantry, D., Dietsch, G.N., Gray, P.W. J. Neuroimmunol. (1995) [Pubmed]
  25. Induction of monocyte- and T-cell-attracting chemokines in the lung during the generation of idiopathic pneumonia syndrome following allogeneic murine bone marrow transplantation. Panoskaltsis-Mortari, A., Strieter, R.M., Hermanson, J.R., Fegeding, K.V., Murphy, W.J., Farrell, C.L., Lacey, D.L., Blazar, B.R. Blood (2000) [Pubmed]
  26. Molecular cloning and functional characterization of a novel member of the C-C chemokine family. Hara, T., Bacon, K.B., Cho, L.C., Yoshimura, A., Morikawa, Y., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Schall, T.J., Miyajima, A. J. Immunol. (1995) [Pubmed]
  27. Role of CC chemokine CCL6/C10 as a monocyte chemoattractant in a murine acute peritonitis. LaFleur, A.M., Lukacs, N.W., Kunkel, S.L., Matsukawa, A. Mediators of inflammation. (2004) [Pubmed]
  28. Do multidrug resistance-associated protein-1 and -2 play any role in the elimination of estradiol-17 beta-glucuronide and 2,4-dinitrophenyl-S-glutathione across the blood-cerebrospinal fluid barrier? Lee, Y.J., Kusuhara, H., Sugiyama, Y. Journal of pharmaceutical sciences. (2004) [Pubmed]
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