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Gene Review

CCL4  -  chemokine (C-C motif) ligand 4

Homo sapiens

Synonyms: ACT-2, ACT2, AT744.1, Act-2, C-C motif chemokine 4, ...
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Disease relevance of CCL4


Psychiatry related information on CCL4


High impact information on CCL4


Chemical compound and disease context of CCL4


Biological context of CCL4


Anatomical context of CCL4


Associations of CCL4 with chemical compounds


Physical interactions of CCL4


Regulatory relationships of CCL4


Other interactions of CCL4


Analytical, diagnostic and therapeutic context of CCL4

  • CC chemokine ligand (CCL)2, CCL3 and CCL4 levels were measured in the bronchoalveolar lavage fluid (BALF) of 18 nonsmoker control subjects and 17 patients affected by IPF [39].
  • A significant difference was observed in MIP-1-beta levels in BALF of chronic bronchitics (8.11+/-5.97 pg x mL(-1)) compared to smoker (3.57+/-2.90 pg x mL(-1), p=0.018), exsmoker (3.43+/-0.68 pg x mL(-1), p=0.025) and nonsmoker (3.39+/-3.73 pg x mL(-1), p=0.008) control groups [40].
  • PCR primers were designed from two genomic GenBank entries to conduct single-strand conformational polymorphism analysis, sequence analysis, and PCR-RFLP, and we conclude that previously isolated clones referred to as MIP-1beta are derived from two genes, originally called ACT-2 and LAG-1 [41].
  • We used immunoassays and bioassays to assess the presence and function of MIP-1 beta using samples obtained from 62 arthritic patients [26].
  • Real-time PCR and conventional RT-PCR revealed significant up-regulation of transcript levels of the trout CCL4-like mRNA in LPS-stimulated in vitro differentiated macrophages [42].


  1. Genetic variation in the CCL18-CCL3-CCL4 chemokine gene cluster influences HIV Type 1 transmission and AIDS disease progression. Modi, W.S., Lautenberger, J., An, P., Scott, K., Goedert, J.J., Kirk, G.D., Buchbinder, S., Phair, J., Donfield, S., O'Brien, S.J., Winkler, C. Am. J. Hum. Genet. (2006) [Pubmed]
  2. Expression of the beta chemokines CCL3, CCL4, CCL5 and their receptors in idiopathic inflammatory myopathies. Civatte, M., Bartoli, C., Schleinitz, N., Chetaille, B., Pellissier, J.F., Figarella-Branger, D. Neuropathol. Appl. Neurobiol. (2005) [Pubmed]
  3. Chemokines in onchocerciasis patients after a single dose of ivermectin. Fendt, J., Hamm, D.M., Banla, M., Schulz-Key, H., Wolf, H., Helling-Giese, G., Heuschkel, C., Soboslay, P.T. Clin. Exp. Immunol. (2005) [Pubmed]
  4. Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes. Schmidtmayerova, H., Nottet, H.S., Nuovo, G., Raabe, T., Flanagan, C.R., Dubrovsky, L., Gendelman, H.E., Cerami, A., Bukrinsky, M., Sherry, B. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  5. A cSNP map and database for human chromosome 21. Deutsch, S., Iseli, C., Bucher, P., Antonarakis, S.E., Scott, H.S. Genome Res. (2001) [Pubmed]
  6. The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. Cocchi, F., DeVico, A.L., Garzino-Demo, A., Cara, A., Gallo, R.C., Lusso, P. Nat. Med. (1996) [Pubmed]
  7. T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1 beta. Tanaka, Y., Adams, D.H., Hubscher, S., Hirano, H., Siebenlist, U., Shaw, S. Nature (1993) [Pubmed]
  8. Estrogen reduces CCL4- induced liver fibrosis in rats. Xu, J.W., Gong, J., Chang, X.M., Luo, J.Y., Dong, L., Hao, Z.M., Jia, A., Xu, G.P. World J. Gastroenterol. (2002) [Pubmed]
  9. Traditional Chinese medicine prevents inflammation in CCl4-related liver injury in mice. Li, M.Y., Ryan, P., Batey, R.G. Am. J. Chin. Med. (2003) [Pubmed]
  10. Antioxidant and protective effect of an oleanolic acid-enriched extract of A. deliciosa root on carbon tetrachloride induced rat liver injury. Bai, X., Qiu, A., Guan, J., Shi, Z. Asia Pacific journal of clinical nutrition (2007) [Pubmed]
  11. The gene encoding the Act-2 cytokine. Genomic structure, HTLV-I/Tax responsiveness of 5' upstream sequences, and chromosomal localization. Napolitano, M., Modi, W.S., Cevario, S.J., Gnarra, J.R., Seuanez, H.N., Leonard, W.J. J. Biol. Chem. (1991) [Pubmed]
  12. Binding of recombinant feline immunodeficiency virus surface glycoprotein to feline cells: role of CXCR4, cell-surface heparans, and an unidentified non-CXCR4 receptor. de Parseval, A., Elder, J.H. J. Virol. (2001) [Pubmed]
  13. Reduced GRK2 level in T cells potentiates chemotaxis and signaling in response to CCL4. Vroon, A., Heijnen, C.J., Lombardi, M.S., Cobelens, P.M., Mayor, F., Caron, M.G., Kavelaars, A. J. Leukoc. Biol. (2004) [Pubmed]
  14. Gene copy number regulates the production of the human chemokine CCL3-L1. Townson, J.R., Barcellos, L.F., Nibbs, R.J. Eur. J. Immunol. (2002) [Pubmed]
  15. Variants of CCR5, which are permissive for HIV-1 infection, show distinct functional responses to CCL3, CCL4 and CCL5. Dong, H.F., Wigmore, K., Carrington, M.N., Dean, M., Turpin, J.A., Howard, O.M. Genes Immun. (2005) [Pubmed]
  16. Altered chemokine levels in individuals at risk of Type 1 diabetes mellitus. Hanifi-Moghaddam, P., Kappler, S., Seissler, J., Müller-Scholze, S., Martin, S., Roep, B.O., Strassburger, K., Kolb, H., Schloot, N.C. Diabet. Med. (2006) [Pubmed]
  17. Immunomonitoring of renal transplant recipients in the early posttransplant period by sequential analysis of chemokine and chemokine receptor gene expression in peripheral blood mononuclear cells. Dalton, R.S., Webber, J.N., Pead, P., Gibbs, P.J., Sadek, S.A., Howell, W.M. Transplant. Proc. (2005) [Pubmed]
  18. HIV-1-suppressive factors are secreted by CD4+ T cells during primary immune responses. Abdelwahab, S.F., Cocchi, F., Bagley, K.C., Kamin-Lewis, R., Gallo, R.C., DeVico, A., Lewis, G.K. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  19. Natural truncation of the chemokine MIP-1 beta /CCL4 affects receptor specificity but not anti-HIV-1 activity. Guan, E., Wang, J., Roderiquez, G., Norcross, M.A. J. Biol. Chem. (2002) [Pubmed]
  20. Selective induction of Th2-attracting chemokines CCL17 and CCL22 in human B cells by latent membrane protein 1 of Epstein-Barr virus. Nakayama, T., Hieshima, K., Nagakubo, D., Sato, E., Nakayama, M., Kawa, K., Yoshie, O. J. Virol. (2004) [Pubmed]
  21. The beta chemokines CCL4 and CCL5 enhance adhesion of specific CD4+ T cell subsets to human brain endothelial cells. Quandt, J., Dorovini-Zis, K. J. Neuropathol. Exp. Neurol. (2004) [Pubmed]
  22. Chemokine production by G protein-coupled receptor activation in a human mast cell line: roles of extracellular signal-regulated kinase and NFAT. Ali, H., Ahamed, J., Hernandez-Munain, C., Baron, J.L., Krangel, M.S., Patel, D.D. J. Immunol. (2000) [Pubmed]
  23. Chemokines of the alpha, beta-subclass inhibit human basophils' responsiveness to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1. Kuna, P., Reddigari, S.R., Rucinski, D., Schall, T.J., Kaplan, A.P. J. Allergy Clin. Immunol. (1995) [Pubmed]
  24. Serum levels of chemokines correlate with disease activity in patients with retinal vasculitis. Wallace, G.R., Farmer, I., Church, A., Graham, E.M., Stanford, M.R. Immunol. Lett. (2003) [Pubmed]
  25. Chemokine-dependent upregulation of CD11b on specific leukocyte subpopulations in human whole blood: effect of anticoagulant on rantes and MIP-1 beta stimulation. Conklyn, M.J., Neote, K., Showell, H.J. Cytokine (1996) [Pubmed]
  26. Macrophage inflammatory protein-1 beta: a C-C chemokine in osteoarthritis. Koch, A.E., Kunkel, S.L., Shah, M.R., Fu, R., Mazarakis, D.D., Haines, G.K., Burdick, M.D., Pope, R.M., Strieter, R.M. Clin. Immunol. Immunopathol. (1995) [Pubmed]
  27. Macrophage inflammatory protein-1beta induces migration and activation of human thymocytes. Dairaghi, D.J., Franz-Bacon, K., Callas, E., Cupp, J., Schall, T.J., Tamraz, S.A., Boehme, S.A., Taylor, N., Bacon, K.B. Blood (1998) [Pubmed]
  28. Cholesterol is essential for macrophage inflammatory protein 1 beta binding and conformational integrity of CC chemokine receptor 5. Nguyen, D.H., Taub, D. Blood (2002) [Pubmed]
  29. Functional redundancy of the human CCL4 and CCL4L1 chemokine genes. Howard, O.M., Turpin, J.A., Goldman, R., Modi, W.S. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  30. Morphine enhances HIV infection of neonatal macrophages. Li, Y., Merrill, J.D., Mooney, K., Song, L., Wang, X., Guo, C.J., Savani, R.C., Metzger, D.S., Douglas, S.D., Ho, W.Z. Pediatr. Res. (2003) [Pubmed]
  31. Macrophage inflammatory protein (MIP)-1 beta abrogates the capacity of MIP-1 alpha to suppress myeloid progenitor cell growth. Broxmeyer, H.E., Sherry, B., Cooper, S., Ruscetti, F.W., Williams, D.E., Arosio, P., Kwon, B.S., Cerami, A. J. Immunol. (1991) [Pubmed]
  32. Role of cholesterol in human immunodeficiency virus type 1 envelope protein-mediated fusion with host cells. Viard, M., Parolini, I., Sargiacomo, M., Fecchi, K., Ramoni, C., Ablan, S., Ruscetti, F.W., Wang, J.M., Blumenthal, R. J. Virol. (2002) [Pubmed]
  33. Activating transcription factor 3 (ATF3) represses the expression of CCL4 in murine macrophages. Khuu, C.H., Barrozo, R.M., Hai, T., Weinstein, S.L. Mol. Immunol. (2007) [Pubmed]
  34. Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78beta into a most efficient monocyte attractant and CCR1 agonist. Proost, P., Menten, P., Struyf, S., Schutyser, E., De Meester, I., Van Damme, J. Blood (2000) [Pubmed]
  35. IFN-alpha beta released by Mycobacterium tuberculosis-infected human dendritic cells induces the expression of CXCL10: selective recruitment of NK and activated T cells. Lande, R., Giacomini, E., Grassi, T., Remoli, M.E., Iona, E., Miettinen, M., Julkunen, I., Coccia, E.M. J. Immunol. (2003) [Pubmed]
  36. Cathepsin D specifically cleaves the chemokines macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and SLC that are expressed in human breast cancer. Wolf, M., Clark-Lewis, I., Buri, C., Langen, H., Lis, M., Mazzucchelli, L. Am. J. Pathol. (2003) [Pubmed]
  37. Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells. Megjugorac, N.J., Young, H.A., Amrute, S.B., Olshalsky, S.L., Fitzgerald-Bocarsly, P. J. Leukoc. Biol. (2004) [Pubmed]
  38. Identification of the CC chemokines TARC and macrophage inflammatory protein-1 beta as novel functional ligands for the CCR8 receptor. Bernardini, G., Hedrick, J., Sozzani, S., Luini, W., Spinetti, G., Weiss, M., Menon, S., Zlotnik, A., Mantovani, A., Santoni, A., Napolitano, M. Eur. J. Immunol. (1998) [Pubmed]
  39. CCR5 expression and CC chemokine levels in idiopathic pulmonary fibrosis. Capelli, A., Di Stefano, A., Gnemmi, I., Donner, C.F. Eur. Respir. J. (2005) [Pubmed]
  40. Increased MCP-1 and MIP-1beta in bronchoalveolar lavage fluid of chronic bronchitics. Capelli, A., Di Stefano, A., Gnemmi, I., Balbo, P., Cerutti, C.G., Balbi, B., Lusuardi, M., Donner, C.F. Eur. Respir. J. (1999) [Pubmed]
  41. The human MIP-1beta chemokine is encoded by two paralogous genes, ACT-2 and LAG-1. Modi, W.S., Bergeron, J., Sanford, M. Immunogenetics (2001) [Pubmed]
  42. Characterization of a highly inducible novel CC chemokine from differentiated rainbow trout (Oncorhynchus mykiss) macrophages. Mackenzie, S., Liarte, C., Iliev, D., Planas, J.V., Tort, L., Goetz, F.W. Immunogenetics (2004) [Pubmed]
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