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Gene Review

Ccl5  -  chemokine (C-C motif) ligand 5

Rattus norvegicus

Synonyms: C-C motif chemokine 5, Rantes, SIS-delta, Scya5, Small-inducible cytokine A5, ...
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Disease relevance of Ccl5


High impact information on Ccl5

  • In contrast to the consequences of MCP-1 binding, we were unable to demonstrate ligand-dependent calcium fluxes on binding of Rantes to human monocytes or THP-1 cells [5].
  • Receptor affinity for Rantes is enhanced on preparation of isolated membranes with a 12-fold decrease in receptor Kd [5].
  • These findings were associated with a reduction in eotaxin mRNA and an increase in mRNA for the T-cell chemokines macrophage inflammatory protein-2 (MIP-2), MIP-1beta, and RANTES [6].
  • Sequential cytokine dynamics in chronic rejection of rat renal allografts: roles for cytokines RANTES and MCP-1 [7].
  • RANTES (regulated upon activation, normal T-cell expressed and secreted) peaked at 2 weeks; intercellular adhesion molecule (ICAM-1) was maximally expressed at 6 weeks [7].

Chemical compound and disease context of Ccl5


Biological context of Ccl5

  • CCR3, another RANTES/CCL5 receptor, was constitutively high on macrophages in vivo and in vitro, with down-regulation during AIA [10].
  • The gene expression of monocyte chemattractant protein-1 (MCP-1) and regulated upon activation, normal T cell expressed and secreted (RANTES) was markedly reduced in tacrolimus-treated eyes [11].
  • These data show that chemotaxis for GILs is upregulated locally during lung allograft rejection, and that MCP-1 and RANTES contribute to GIL recruitment during the rejection response [12].
  • The lymphocyte chemoattractant RANTES had delayed kinetics, with a rise at Day 3, a peak at Day 4, and a gradual decline [13].
  • RANTES seemed to promote diapedesis of adherent Th1-type cells by augmenting pseudopod formation in conjunction with actin rearrangement by a pathway that was sensitive to the phosphoinositol 3-kinase inhibitor wortmannin and to the Rho GTP-binding protein inhibitor, epidermal cell differentiation inhibitor [14].

Anatomical context of Ccl5


Associations of Ccl5 with chemical compounds


Regulatory relationships of Ccl5

  • LPS downregulated the expression of MIP-1alpha and MCP-1 mRNAs and upregulated RANTES mRNA in Kupffer cells at 3-h post endotoxin [19].
  • TNF-alpha also induced RANTES gene expression but LPS did not [20].
  • These results provide strong evidence for the existence of rapid mechanisms in the AH/POA which involve both COX isozymes during the fever induced by RANTES, and further support the existence of an alternative PG-independent pathway in the febrile response [21].
  • Altogether, these results demonstrated that infection of glial cells by JEV provided the early ERK-, NF-kappaB-, and NF-IL-6-mediated signals that directly activated RANTES expression, which might be involved in the initiation and amplification of inflammatory responses in the CNS [22].

Other interactions of Ccl5


Analytical, diagnostic and therapeutic context of Ccl5


  1. Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats. Bless, N.M., Huber-Lang, M., Guo, R.F., Warner, R.L., Schmal, H., Czermak, B.J., Shanley, T.P., Crouch, L.D., Lentsch, A.B., Sarma, V., Mulligan, M.S., Friedl, H.P., Ward, P.A. J. Immunol. (2000) [Pubmed]
  2. Expression of CC chemokines and their receptors in the eye in autoimmune anterior uveitis associated with EAE. Adamus, G., Manczak, M., Machnicki, M. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  3. Chemokine expression in rat stab wound brain injury. Ghirnikar, R.S., Lee, Y.L., He, T.R., Eng, L.F. J. Neurosci. Res. (1996) [Pubmed]
  4. The chemokine RANTES is a crucial mediator of the progression from acute to chronic colitis in the rat. Ajuebor, M.N., Hogaboam, C.M., Kunkel, S.L., Proudfoot, A.E., Wallace, J.L. J. Immunol. (2001) [Pubmed]
  5. Characterization and species distribution of high affinity GTP-coupled receptors for human rantes and monocyte chemoattractant protein 1. Van Riper, G., Siciliano, S., Fischer, P.A., Meurer, R., Springer, M.S., Rosen, H. J. Exp. Med. (1993) [Pubmed]
  6. Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. Spergel, J.M., Mizoguchi, E., Oettgen, H., Bhan, A.K., Geha, R.S. J. Clin. Invest. (1999) [Pubmed]
  7. Sequential cytokine dynamics in chronic rejection of rat renal allografts: roles for cytokines RANTES and MCP-1. Nadeau, K.C., Azuma, H., Tilney, N.L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  8. Acute alcohol intoxication and endotoxemia desensitize HIV-1 gp120-induced CC-chemokine production by Kupffer cells. Bautista, A.P. Life Sci. (2001) [Pubmed]
  9. L-arginine suppresses lipopolysaccharide-induced expression of RANTES in glomeruli. Haberstroh, U., Stilo, K., Pocock, J., Wolf, G., Helmchen, U., Wenzel, U., Zahner, G., Stahl, R.A., Thaiss, F. J. Am. Soc. Nephrol. (1998) [Pubmed]
  10. Chemokine receptor expression in rat adjuvant-induced arthritis. Haas, C.S., Martinez, R.J., Attia, N., Haines, G.K., Campbell, P.L., Koch, A.E. Arthritis Rheum. (2005) [Pubmed]
  11. Intravitreal injection of Tacrolimus (FK506) suppresses ongoing experimental autoimmune uveoretinitis in Rats. Oh-I, K., Keino, H., Goto, H., Yamakawa, N., Murase, K., Usui, Y., Kezuka, T., Sakai, J., Takeuchi, M., Usui, M. The British journal of ophthalmology (2007) [Pubmed]
  12. Monocyte chemoattractant protein-1 and RANTES are chemotactic for graft infiltrating lymphocytes during acute lung allograft rejection. Sekine, Y., Yasufuku, K., Heidler, K.M., Cummings, O.W., Van Rooijen, N., Fujisawa, T., Brown, J., Wilkes, D.S. Am. J. Respir. Cell Mol. Biol. (2000) [Pubmed]
  13. Chemokine expression in nerve allografts. Midha, R., Munro, C.A., Ramakrishna, V., Matsuyama, T., Gorczynski, R.M. Neurosurgery (2004) [Pubmed]
  14. Selective diapedesis of Th1 cells induced by endothelial cell RANTES. Kawai, T., Seki, M., Hiromatsu, K., Eastcott, J.W., Watts, G.F., Sugai, M., Smith, D.J., Porcelli, S.A., Taubman, M.A. J. Immunol. (1999) [Pubmed]
  15. Impact of Rantes and MCP-1 chemokines on in vivo basophilic cell recruitment in rat skin injection model and their role in modifying the protein and mRNA levels for histidine decarboxylase. Conti, P., Pang, X., Boucher, W., Letourneau, R., Reale, M., Barbacane, R.C., Thibault, J., Theoharides, T.C. Blood (1997) [Pubmed]
  16. Cyclooxygenase metabolites mediate glomerular monocyte chemoattractant protein-1 formation and monocyte recruitment in experimental glomerulonephritis. Schneider, A., Harendza, S., Zahner, G., Jocks, T., Wenzel, U., Wolf, G., Thaiss, F., Helmchen, U., Stahl, R.A. Kidney Int. (1999) [Pubmed]
  17. DNA vaccination with naked DNA encoding MCP-1 and RANTES protects against renal injury in adriamycin nephropathy. Wu, H., Wang, Y., Tay, Y.C., Zheng, G., Zhang, C., Alexander, S.I., Harris, D.C. Kidney Int. (2005) [Pubmed]
  18. RANTES: a new prostaglandin dependent endogenous pyrogen in the rat. Tavares, E., Miñano, F.J. Neuropharmacology (2000) [Pubmed]
  19. Acute alcohol intoxication and gadolinium chloride attenuate endotoxin-induced release of CC chemokines in the rat. Bukara, M., Bautista, A.P. Alcohol (2000) [Pubmed]
  20. Chemokines, osteopontin, ICAM-1 gene expression in cultured rat mesangial cells. Lee, S.K., Park, J.Y., Chung, S.J., Yang, W.S., Kim, S.B., Park, S.K., Park, J.S. J. Korean Med. Sci. (1998) [Pubmed]
  21. Differential sensitivities of pyrogenic chemokine fevers to cyclooxygenase isozymes antibodies. Tavares, E., Miñano, F.J. Brain Res. Bull. (2002) [Pubmed]
  22. Upregulation of RANTES gene expression in neuroglia by Japanese encephalitis virus infection. Chen, C.J., Chen, J.H., Chen, S.Y., Liao, S.L., Raung, S.L. J. Virol. (2004) [Pubmed]
  23. The pathogenesis of pulmonary contusion: an open chest model in the rat. Hoth, J.J., Stitzel, J.D., Gayzik, F.S., Brownlee, N.A., Miller, P.R., Yoza, B.K., McCall, C.E., Meredith, J.W., Payne, R.M. The Journal of trauma. (2006) [Pubmed]
  24. Chemotaxis of alveolar macrophages in response to signals derived from alveolar epithelial cells. O'Brien, A.D., Standiford, T.J., Christensen, P.J., Wilcoxen, S.E., Paine, R. J. Lab. Clin. Med. (1998) [Pubmed]
  25. Identification of cell types producing RANTES, MIP-1 alpha and MIP-1 beta in rat experimental autoimmune encephalomyelitis by in situ hybridization. Miyagishi, R., Kikuchi, S., Takayama, C., Inoue, Y., Tashiro, K. J. Neuroimmunol. (1997) [Pubmed]
  26. Oral administration of cholera toxin B subunit conjugated to myelin basic protein protects against experimental autoimmune encephalomyelitis by inducing transforming growth factor-beta-secreting cells and suppressing chemokine expression. Sun, J.B., Xiao, B.G., Lindblad, M., Li, B.L., Link, H., Czerkinsky, C., Holmgren, J. Int. Immunol. (2000) [Pubmed]
  27. Gene transfer of RANTES and MCP-1 chemokine antagonists prolongs cardiac allograft survival. Fleury, S., Li, J., Simeoni, E., Fiorini, E., von Segesser, L.K., Kappenberger, L., Vassalli, G. Gene Ther. (2006) [Pubmed]
  28. Long-lasting protective immunity to experimental autoimmune encephalomyelitis following vaccination with naked DNA encoding C-C chemokines. Youssef, S., Wildbaum, G., Maor, G., Lanir, N., Gour-Lavie, A., Grabie, N., Karin, N. J. Immunol. (1998) [Pubmed]
  29. Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage. Sun, D., Tani, M., Newman, T.A., Krivacic, K., Phillips, M., Chernosky, A., Gill, P., Wei, T., Griswold, K.J., Ransohoff, R.M., Weller, R.O. J. Neuropathol. Exp. Neurol. (2000) [Pubmed]
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