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Chemokine (C-C motif) ligand 4, also known as CCL4, is a protein which in humans is encoded by the CCL4 gene.[1]


CCL4, also known as Macrophage inflammatory protein-1β (MIP-1β) is a CC chemokine with specificity for CCR5 receptors. It is a chemoattractant for natural killer cells, monocytes and a variety of other immune cells.[2]

CCL4 is a major HIV-suppressive factor produced by CD8+ T cells.[3]

Perforin-low memory CD8+ T cells that normally synthesize MIP-1-beta.[4]

CCL4 is produced by: monocytes, B cells, T cells, fibroblasts, endothelial cells, and epithelial cells.[5]

Concentration of this chemokine has been shown to be inversely related with MicroRNA-125b. Concentration of CCL4 within the body increases with age, which may cause chronic inflammation and liver damage.[5][6]


CCL4 has been shown to interact with CCL3.[7]

CCL4 binds to G protein-Coupled Receptors CCR5 and CCR8.[5]

See also


  1. Irving SG, Zipfel PF, Balke J, McBride OW, Morton CC, Burd PR, Siebenlist U, Kelly K (June 1990). "Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q". Nucleic Acids Research. 18 (11): 3261–70. doi:10.1093/nar/18.11.3261. PMC 330932. PMID 1972563.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  2. Bystry RS, Aluvihare V, Welch KA, Kallikourdis M, Betz AG (December 2001). "B cells and professional APCs recruit regulatory T cells via CCL4". Nature Immunology. 2 (12): 1126–32. doi:10.1038/ni735. PMID 11702067.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  3. Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P (December 1995). "Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells". Science. 270 (5243): 1811–5. doi:10.1126/science.270.5243.1811. PMID 8525373.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  4. Kamin-Lewis R, Abdelwahab SF, Trang C, Baker A, DeVico AL, Gallo RC, Lewis GK (July 2001). "Perforin-low memory CD8+ cells are the predominant T cells in normal humans that synthesize the beta -chemokine macrophage inflammatory protein-1beta". Proceedings of the National Academy of Sciences of the United States of America. 98 (16): 9283–8. doi:10.1073/pnas.161298998. PMC 55412. PMID 11470920.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  5. 5.0 5.1 5.2 Morrison MD, Lundquist PG (April 1974). "Labyrinthine morphology and temperature in cryosurgery (guinea pig)". Acta Oto-Laryngologica. 77 (4): 261–73. PMC 4364832.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  6. Morimoto T, Takagi H, Kondo T (January 1985). "Canine pancreatic allotransplantation with duodenum (pancreaticoduodenal transplantation) using cyclosporin A". Nagoya Journal of Medical Science. 47 (1–2): 57–66. PMC 3887178.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  7. Guan E, Wang J, Norcross MA (April 2001). "Identification of human macrophage inflammatory proteins 1alpha and 1beta as a native secreted heterodimer". The Journal of Biological Chemistry. 276 (15): 12404–9. doi:10.1074/jbc.M006327200. PMID 11278300.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

Further reading

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  • Menten P, Wuyts A, Van Damme J (December 2002). "Macrophage inflammatory protein-1". Cytokine & Growth Factor Reviews. 13 (6): 455–81. doi:10.1016/S1359-6101(02)00045-X. PMID 12401480.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Muthumani K, Desai BM, Hwang DS, Choo AY, Laddy DJ, Thieu KP, Rao RG, Weiner DB (April 2004). "HIV-1 Vpr and anti-inflammatory activity". DNA and Cell Biology. 23 (4): 239–47. doi:10.1089/104454904773819824. PMID 15142381.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Conti L, Fantuzzi L, Del Cornò M, Belardelli F, Gessani S (2005). "Immunomodulatory effects of the HIV-1 gp120 protein on antigen presenting cells: implications for AIDS pathogenesis". Immunobiology. 209 (1–2): 99–115. doi:10.1016/j.imbio.2004.02.008. PMID 15481145.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Joseph AM, Kumar M, Mitra D (January 2005). "Nef: "necessary and enforcing factor" in HIV infection". Current HIV Research. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Zhao RY, Elder RT (March 2005). "Viral infections and cell cycle G2/M regulation". Cell Research. 15 (3): 143–9. doi:10.1038/ PMID 15780175.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Zhao RY, Bukrinsky M, Elder RT (April 2005). "HIV-1 viral protein R (Vpr) & host cellular responses". The Indian Journal of Medical Research. 121 (4): 270–86. PMID 15817944.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Research. 15 (11–12): 923–34. doi:10.1038/ PMID 16354571.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • King JE, Eugenin EA, Buckner CM, Berman JW (April 2006). "HIV tat and neurotoxicity". Microbes and Infection. 8 (5): 1347–57. doi:10.1016/j.micinf.2005.11.014. PMID 16697675.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Napolitano M, Modi WS, Cevario SJ, Gnarra JR, Seuanez HN, Leonard WJ (September 1991). "The gene encoding the Act-2 cytokine. Genomic structure, HTLV-I/Tax responsiveness of 5' upstream sequences, and chromosomal localization". The Journal of Biological Chemistry. 266 (26): 17531–6. PMID 1894635.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Irving SG, Zipfel PF, Balke J, McBride OW, Morton CC, Burd PR, Siebenlist U, Kelly K (June 1990). "Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q". Nucleic Acids Research. 18 (11): 3261–70. doi:10.1093/nar/18.11.3261. PMC 330932. PMID 1972563.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Baixeras E, Roman-Roman S, Jitsukawa S, Genevee C, Mechiche S, Viegas-Pequignot E, Hercend T, Triebel F (November 1990). "Cloning and expression of a lymphocyte activation gene (LAG-1)". Molecular Immunology. 27 (11): 1091–102. doi:10.1016/0161-5890(90)90097-J. PMID 2247088.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Lipes MA, Napolitano M, Jeang KT, Chang NT, Leonard WJ (December 1988). "Identification, cloning, and characterization of an immune activation gene". Proceedings of the National Academy of Sciences of the United States of America. 85 (24): 9704–8. doi:10.1073/pnas.85.24.9704. PMC 282843. PMID 2462251.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Brown KD, Zurawski SM, Mosmann TR, Zurawski G (January 1989). "A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes". Journal of Immunology. 142 (2): 679–87. PMID 2521353.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Zipfel PF, Balke J, Irving SG, Kelly K, Siebenlist U (March 1989). "Mitogenic activation of human T cells induces two closely related genes which share structural similarities with a new family of secreted factors". Journal of Immunology. 142 (5): 1582–90. PMID 2521882.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Chang HC, Reinherz EL (June 1989). "Isolation and characterization of a cDNA encoding a putative cytokine which is induced by stimulation via the CD2 structure on human T lymphocytes". European Journal of Immunology. 19 (6): 1045–51. doi:10.1002/eji.1830190614. PMID 2568930.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Miller MD, Hata S, De Waal Malefyt R, Krangel MS (November 1989). "A novel polypeptide secreted by activated human T lymphocytes". Journal of Immunology. 143 (9): 2907–16. PMID 2809212.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O (September 1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature. 377 (6547 Suppl): 3–174. PMID 7566098.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Post TW, Bozic CR, Rothenberg ME, Luster AD, Gerard N, Gerard C (December 1995). "Molecular characterization of two murine eosinophil beta chemokine receptors". Journal of Immunology. 155 (11): 5299–305. PMID 7594543.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Combadiere C, Ahuja SK, Murphy PM (July 1995). "Cloning and functional expression of a human eosinophil CC chemokine receptor". The Journal of Biological Chemistry. 270 (28): 16491–4. doi:10.1074/jbc.270.28.16491. PMID 7622448.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Paolini JF, Willard D, Consler T, Luther M, Krangel MS (September 1994). "The chemokines IL-8, monocyte chemoattractant protein-1, and I-309 are monomers at physiologically relevant concentrations". Journal of Immunology. 153 (6): 2704–17. PMID 8077676.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

External links