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Gene Review

Ccl5  -  chemokine (C-C motif) ligand 5

Mus musculus

Synonyms: C-C motif chemokine 5, MuRantes, RANTES, SIS-delta, SISd, ...
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Disease relevance of Ccl5


High impact information on Ccl5

  • The protective effect of Ccl5 requires activation of the Ccr5 chemokine receptor and consequent bilateral activation of G(alphai)-PI3K-AKT and G(alphai)-MEK-ERK signaling pathways [5].
  • Virus-inducible levels of Ccl5 are required to prevent apoptosis of virus-infected mouse macrophages in vivo and mouse and human macrophages ex vivo [5].
  • RANTES production by memory phenotype T cells is controlled by a posttranscriptional, TCR-dependent process [6].
  • An examination of differences in gene expression between memory and naive phenotype T cells revealed elevated levels of mRNA for several chemokines, especially RANTES, in memory phenotype T cells [6].
  • In vivo, CD8+ memory T cells proliferate continuously and slowly in response to IL-15; however, IL-15 does not stimulate RANTES secretion [6].

Chemical compound and disease context of Ccl5


Biological context of Ccl5

  • Serial Analysis of Gene Expression in Progressing and Regressing Mouse Tumors Implicates the Involvement of RANTES and TARC in Antitumor Immune Responses [12].
  • In contrast, mutation of the other two putative NF-kappaB binding sites did not affect RANTES promoter activity significantly [13].
  • In vitro chemotaxis assays confirmed that lung lavage fluid from MHV-68-infected mice had chemotactic activity, which was partially blocked by antibodies to IP-10 and RANTES [14].
  • Airway eosinophilia, OVA-specific IgE in serum, and chemokine eotaxin and RANTES (regulated upon activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid were measured by lung histology, Diff-Quick staining, and ELISA [15].
  • The protein-coding region of this cDNA is 73, 71, 50, and 48% identical in nucleic acid sequence to those of human macrophage chemoattractant protein (MCP) 3, MCP-1, macrophage inflammatory protein (MIP) 1 alpha, and RANTES, respectively [16].

Anatomical context of Ccl5


Associations of Ccl5 with chemical compounds


Enzymatic interactions of Ccl5


Co-localisations of Ccl5


Regulatory relationships of Ccl5

  • This study uncovers a novel IFNgamma-induced pathway in RANTES expression mediated by IRF-1 in macrophages and elucidates an important host defense mechanism against neoplastic transformation [27].
  • Adenovirus-mediated gene transduction of IRF-1 in primary macrophages resulted in enhanced RANTES expression [27].
  • IRF-8 can activate RANTES gene transcription in synergism with IRF-1 [20].
  • Treatment with RANTES specifically modulated astrocyte receptors upregulating intercellular adhesion molecule 1 (ICAM-1) and downregulating CX3CR1 expression [28].
  • Intrarenal CCL5 production was enhanced by Flt3L administration, in association with marked increases in interstitial CD45+ mononuclear cells [29].

Other interactions of Ccl5

  • RANTES-mediated chemokine amplification in DC may prolong inflammatory responses and shape the microenvironment, potentially enhancing acquired and innate immune responses [17].
  • TNF-alpha-treated DC lose responsiveness to RANTES [17].
  • Interferon regulatory factor 1 is an essential and direct transcriptional activator for interferon {gamma}-induced RANTES/CCl5 expression in macrophages [27].
  • After initiating GN, MCP-1 and RANTES and their receptors are readily downregulated [30].
  • TNFR1-/- mice with EAE had significantly higher expression of CXCL10 mRNA (but not CCL5 mRNA) in the CNS compared to WT mice with EAE [31].

Analytical, diagnostic and therapeutic context of Ccl5


  1. CCL5 modulates pneumococcal immunity and carriage. Palaniappan, R., Singh, S., Singh, U.P., Singh, R., Ades, E.W., Briles, D.E., Hollingshead, S.K., Royal, W., Sampson, J.S., Stiles, J.K., Taub, D.D., Lillard, J.W. J. Immunol. (2006) [Pubmed]
  2. Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1alpha and monocyte chemotactic protein-1. Kennedy, K.J., Strieter, R.M., Kunkel, S.L., Lukacs, N.W., Karpus, W.J. J. Neuroimmunol. (1998) [Pubmed]
  3. Contrasting roles for RANTES and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in a murine model of allergic peritonitis. Das, A.M., Ajuebor, M.N., Flower, R.J., Perretti, M., McColl, S.R. Clin. Exp. Immunol. (1999) [Pubmed]
  4. Regulated on activation, normal T cell expressed and secreted (RANTES) antagonist (Met-RANTES) controls the early phase of Trypanosoma cruzi-elicited myocarditis. Marino, A.P., da Silva, A., dos Santos, P., Pinto, L.M., Gazzinelli, R.T., Teixeira, M.M., Lannes-Vieira, J. Circulation (2004) [Pubmed]
  5. CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Tyner, J.W., Uchida, O., Kajiwara, N., Kim, E.Y., Patel, A.C., O'Sullivan, M.P., Walter, M.J., Schwendener, R.A., Cook, D.N., Danoff, T.M., Holtzman, M.J. Nat. Med. (2005) [Pubmed]
  6. RANTES production by memory phenotype T cells is controlled by a posttranscriptional, TCR-dependent process. Swanson, B.J., Murakami, M., Mitchell, T.C., Kappler, J., Marrack, P. Immunity (2002) [Pubmed]
  7. Hmgi-c-independent Activation of MuRantes in Vivo. Schiltz, J.F., Kesari, K., Ashar, H.R., Chada, K. Cell Growth Differ. (2002) [Pubmed]
  8. Treatment of cockroach allergen asthma model with imatinib attenuates airway responses. Berlin, A.A., Lukacs, N.W. Am. J. Respir. Crit. Care Med. (2005) [Pubmed]
  9. TARC and RANTES, but not CTACK, are induced in two models of allergic contact dermatitis. Effects of cilomilast and diflorasone diacetate on T-cell-attracting chemokines. Bäumer, W., Seegers, U., Braun, M., Tschernig, T., Kietzmann, M. Br. J. Dermatol. (2004) [Pubmed]
  10. Chemokines and TRANCE as genetic adjuvants for a DNA vaccine to rabies virus. Pinto, A.R., Reyes-Sandoval, A., Ertl, H.C. Cell. Immunol. (2003) [Pubmed]
  11. Effects of steroid treatment on lung CC chemokines, apoptosis and transepithelial cell clearance during development and resolution of allergic airway inflammation. Uller, L., Lloyd, C.M., Rydell-Törmänen, K., Persson, C.G., Erjefält, J.S. Clin. Exp. Allergy (2006) [Pubmed]
  12. Serial Analysis of Gene Expression in Progressing and Regressing Mouse Tumors Implicates the Involvement of RANTES and TARC in Antitumor Immune Responses. Nakazaki, Y., Hase, H., Inoue, H., Beppu, Y., Meng, X.K., Sakaguchi, G., Kurita, R., Asano, S., Nakamura, Y., Tani, K. Mol. Ther. (2006) [Pubmed]
  13. Tumour necrosis factor-alpha and interferon-gamma synergistically activate the RANTES promoter through nuclear factor kappaB and interferon regulatory factor 1 (IRF-1) transcription factors. Lee, A.H., Hong, J.H., Seo, Y.S. Biochem. J. (2000) [Pubmed]
  14. Chemokine induction and leukocyte trafficking to the lungs during murine gammaherpesvirus 68 (MHV-68) infection. Sarawar, S.R., Lee, B.J., Anderson, M., Teng, Y.C., Zuberi, R., Von Gesjen, S. Virology (2002) [Pubmed]
  15. Arsenic trioxide, a potent inhibitor of NF-kappaB, abrogates allergen-induced airway hyperresponsiveness and inflammation. Zhou, L.F., Zhu, Y., Cui, X.F., Xie, W.P., Hu, A.H., Yin, K.S. Respir. Res. (2006) [Pubmed]
  16. Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung. Rothenberg, M.E., Luster, A.D., Lilly, C.M., Drazen, J.M., Leder, P. J. Exp. Med. (1995) [Pubmed]
  17. RANTES-induced chemokine cascade in dendritic cells. Fischer, F.R., Luo, Y., Luo, M., Santambrogio, L., Dorf, M.E. J. Immunol. (2001) [Pubmed]
  18. Obstructive nephropathy in the mouse: progressive fibrosis correlates with tubulointerstitial chemokine expression and accumulation of CC chemokine receptor 2- and 5-positive leukocytes. Vielhauer, V., Anders, H.J., Mack, M., Cihak, J., Strutz, F., Stangassinger, M., Luckow, B., Gröne, H.J., Schlöndorff, D. J. Am. Soc. Nephrol. (2001) [Pubmed]
  19. Chemokine expression during the development and resolution of a pulmonary leukocyte response to influenza A virus infection in mice. Wareing, M.D., Lyon, A.B., Lu, B., Gerard, C., Sarawar, S.R. J. Leukoc. Biol. (2004) [Pubmed]
  20. Interferon regulatory factor 8 regulates RANTES gene transcription in cooperation with interferon regulatory factor-1, NF-kappaB, and PU.1. Liu, J., Ma, X. J. Biol. Chem. (2006) [Pubmed]
  21. Vitamin C deficiency increases the lung pathology of influenza virus-infected gulo-/- mice. Li, W., Maeda, N., Beck, M.A. J. Nutr. (2006) [Pubmed]
  22. Cloning, genomic organization, and chromosomal localization of the Scya5 gene encoding the murine chemokine RANTES. Danoff, T.M., Lalley, P.A., Chang, Y.S., Heeger, P.S., Neilson, E.G. J. Immunol. (1994) [Pubmed]
  23. RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge. Koya, T., Takeda, K., Kodama, T., Miyahara, N., Matsubara, S., Balhorn, A., Joetham, A., Dakhama, A., Gelfand, E.W. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  24. Expression of chemokine genes during rejection and long-term acceptance of cardiac allografts. Fairchild, R.L., VanBuskirk, A.M., Kondo, T., Wakely, M.E., Orosz, C.G. Transplantation (1997) [Pubmed]
  25. RANTES-mediated chemokine transcription in astrocytes involves activation and translocation of p90 ribosomal S6 protein kinase (RSK). Zhang, Y., Zhai, Q., Luo, Y., Dorf, M.E. J. Biol. Chem. (2002) [Pubmed]
  26. CD8+ T cells produce RANTES during acute rejection of murine allogeneic skin grafts. Koga, S., Novick, A.C., Toma, H., Fairchild, R.L. Transplantation (1999) [Pubmed]
  27. Interferon regulatory factor 1 is an essential and direct transcriptional activator for interferon {gamma}-induced RANTES/CCl5 expression in macrophages. Liu, J., Guan, X., Ma, X. J. Biol. Chem. (2005) [Pubmed]
  28. RANTES stimulates inflammatory cascades and receptor modulation in murine astrocytes. Luo, Y., Berman, M.A., Zhai, Q., Fischer, F.R., Abromson-Leeman, S.R., Zhang, Y., Kuziel, W.A., Gerard, C., Dorf, M.E. Glia (2002) [Pubmed]
  29. CCR and CC chemokine expression in relation to Flt3 ligand-induced renal dendritic cell mobilization. Coates, P.T., Colvin, B.L., Ranganathan, A., Duncan, F.J., Lan, Y.Y., Shufesky, W.J., Zahorchak, A.F., Morelli, A.E., Thomson, A.W. Kidney Int. (2004) [Pubmed]
  30. Chemokine and chemokine receptor expression during initiation and resolution of immune complex glomerulonephritis. Anders, H.J., Vielhauer, V., Kretzler, M., Cohen, C.D., Segerer, S., Luckow, B., Weller, L., Gröne, H.J., Schlöndorff, D. J. Am. Soc. Nephrol. (2001) [Pubmed]
  31. Elevated interferon gamma expression in the central nervous system of tumour necrosis factor receptor 1-deficient mice with experimental autoimmune encephalomyelitis. Wheeler, R.D., Zehntner, S.P., Kelly, L.M., Bourbonnière, L., Owens, T. Immunology (2006) [Pubmed]
  32. beta-Chemokines enhance parasite uptake and promote nitric oxide-dependent microbiostatic activity in murine inflammatory macrophages infected with Trypanosoma cruzi. Aliberti, J.C., Machado, F.S., Souto, J.T., Campanelli, A.P., Teixeira, M.M., Gazzinelli, R.T., Silva, J.S. Infect. Immun. (1999) [Pubmed]
  33. Induction of chemokine gene expression during allogeneic skin graft rejection. Kondo, T., Novick, A.C., Toma, H., Fairchild, R.L. Transplantation (1996) [Pubmed]
  34. Chemokine gene expression during Pneumocystis carinii-driven pulmonary inflammation. Wright, T.W., Johnston, C.J., Harmsen, A.G., Finkelstein, J.N. Infect. Immun. (1999) [Pubmed]
  35. Isolation and characterization of cDNA from renal tubular epithelium encoding murine Rantes. Heeger, P., Wolf, G., Meyers, C., Sun, M.J., O'Farrell, S.C., Krensky, A.M., Neilson, E.G. Kidney Int. (1992) [Pubmed]
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