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Gene Review

Ccl4  -  chemokine (C-C motif) ligand 4

Mus musculus

Synonyms: ACT-2, ACT2, AT744.1, Act-2, C-C motif chemokine 4, ...
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Disease relevance of Ccl4


High impact information on Ccl4


Biological context of Ccl4


Anatomical context of Ccl4

  • We demonstrate that PA is a potent activator of the inflammatory chemokines MIP (macrophage inflammatory protein)-1 alpha and MIP-1 beta (MIPs) mRNA expression in mouse macrophages in a dose- and time-dependent fashion and through a de novo protein synthesis-dependent process [7].
  • Finally, the expression of these new receptors appears to have an effect on activation and degranulation because MIP-1beta (CCL4) and TCA-3 (CCL1) induce significant levels of LTC4 from elicited eosinophils [12].
  • We described previously the inhibitory effect of PGE(2) on the expression and release of the inflammatory chemokines CCL3 and CCL4 from activated dendritic cells [13].
  • Instead, the lower early expression of the neutrophil chemoattractants MIP-1 beta and MIP-2 in the lungs of beige mice tends to suggest that the enhanced susceptibility of these mice to M. avium infection may be due in part to defective recruitment of neutrophils or other cells responsive to these specific chemokines [14].
  • This inhibition is not specific to MIP-1 alpha in that expression of MIP-1 beta, a related molecule that does not exhibit potent stem cell inhibitory properties, is inhibited in a similar manner [15].

Associations of Ccl4 with chemical compounds


Physical interactions of Ccl4

  • An ATF/CREB-binding site is essential for cell-specific and inducible transcription of the murine MIP-1 beta cytokine gene [20].
  • Importantly, purified D6 retains full functional activity, shown by displaceable binding of 125I-labelled MIP-1beta (macrophage inflammatory protein-1beta) and by complete binding of the receptor to a MIP-1alpha affinity column [21].

Regulatory relationships of Ccl4


Other interactions of Ccl4

  • Altered thymocyte migration during experimental acute Trypanosoma cruzi infection: combined role of fibronectin and the chemokines CXCL12 and CCL4 [22].
  • Although GM+ mice are able to express the chemokine RANTES, they lack the ability to express other inflammatory chemokines such as lymphotactin and MIP-1beta [23].
  • However, over the first few weeks of the infection, when the susceptibility of the beige mouse lung first becomes evident, MIP-1 beta and MIP-2 chemokine expression in the lungs was lower in beige mice than in wild-type animals [14].
  • We report here the resolution of MIP-1 into component peptides by SDS-hydroxylapatite chromatography, and compare the NH2-terminal sequences of the two peptides, now referred to as MIP-1 alpha and MIP-1 beta [8].
  • Furthermore, these spleen cells produce cytokines including interleukin(IL)-2, IL-3, interferon-gamma, granulocyte/macrophage colony-stimulating factor, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, which may play an important role in the attraction of mononuclear cells to an antigen-challenging site [24].

Analytical, diagnostic and therapeutic context of Ccl4


  1. Increased expression of MIP-1 alpha and MIP-1 beta mRNAs in the brain correlates spatially and temporally with the spongiform neurodegeneration induced by a murine oncornavirus. Askovic, S., Favara, C., McAtee, F.J., Portis, J.L. J. Virol. (2001) [Pubmed]
  2. Novel immunotherapy for peritoneal dissemination of murine colon cancer with macrophage inflammatory protein-1beta mediated by a tumor-specific vector, HVJ cationic liposomes. Miyata, T., Yamamoto, S., Sakamoto, K., Morishita, R., Kaneda, Y. Cancer Gene Ther. (2001) [Pubmed]
  3. Behavior of hemopoietic stem cells (CFU-S) of mice acutely poisoned with carbon tetrachloride (CC14). Yoshida, K., Yamaguchi, A., Fukuda, M., Shibata, A. Tohoku J. Exp. Med. (1977) [Pubmed]
  4. A key role for ICAM-1 in generating effector cells mediating inflammatory responses. Camacho, S.A., Heath, W.R., Carbone, F.R., Sarvetnick, N., LeBon, A., Karlsson, L., Peterson, P.A., Webb, S.R. Nat. Immunol. (2001) [Pubmed]
  5. B cells and professional APCs recruit regulatory T cells via CCL4. Bystry, R.S., Aluvihare, V., Welch, K.A., Kallikourdis, M., Betz, A.G. Nat. Immunol. (2001) [Pubmed]
  6. Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. Walmsley, S.R., Print, C., Farahi, N., Peyssonnaux, C., Johnson, R.S., Cramer, T., Sobolewski, A., Condliffe, A.M., Cowburn, A.S., Johnson, N., Chilvers, E.R. J. Exp. Med. (2005) [Pubmed]
  7. The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1 alpha and -1 beta in macrophages. Bosco, M.C., Rapisarda, A., Massazza, S., Melillo, G., Young, H., Varesio, L. J. Immunol. (2000) [Pubmed]
  8. Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta. Sherry, B., Tekamp-Olson, P., Gallegos, C., Bauer, D., Davatelis, G., Wolpe, S.D., Masiarz, F., Coit, D., Cerami, A. J. Exp. Med. (1988) [Pubmed]
  9. Estrogen regulates CCR gene expression and function in T lymphocytes. Mo, R., Chen, J., Grolleau-Julius, A., Murphy, H.S., Richardson, B.C., Yung, R.L. J. Immunol. (2005) [Pubmed]
  10. Differential regulation of interleukin-6, macrophage inflammatory protein-1, and JE/MCP-1 cytokine expression in macrophage cell lines. Martin, C.A., Dorf, M.E. Cell. Immunol. (1991) [Pubmed]
  11. Interferon regulatory factor-1 down-regulates cytokine-induced IP-10 expression in pancreatic islets. Baker, M.S., Chen, X., Rotramel, A.R., Nelson, J.J., Kaufman, D.B. Surgery (2003) [Pubmed]
  12. Increased responsiveness of murine eosinophils to MIP-1beta (CCL4) and TCA-3 (CCL1) is mediated by their specific receptors, CCR5 and CCR8. Oliveira, S.H., Lira, S., Martinez-A, C., Wiekowski, M., Sullivan, L., Lukacs, N.W. J. Leukoc. Biol. (2002) [Pubmed]
  13. A novel signaling pathway mediates the inhibition of CCL3/4 expression by prostaglandin E2. Jing, H., Yen, J.H., Ganea, D. J. Biol. Chem. (2004) [Pubmed]
  14. Evidence for a reduced chemokine response in the lungs of beige mice infected with Mycobacterium avium. Florido, M., Appelberg, R., Orme, I.M., Cooper, A.M. Immunology (1997) [Pubmed]
  15. Transforming growth factor beta: is it a downregulator of stem cell inhibition by macrophage inflammatory protein 1 alpha? Maltman, J., Pragnell, I.B., Graham, G.J. J. Exp. Med. (1993) [Pubmed]
  16. Prostaglandin E2 inhibits production of the inflammatory chemokines CCL3 and CCL4 in dendritic cells. Jing, H., Vassiliou, E., Ganea, D. J. Leukoc. Biol. (2003) [Pubmed]
  17. Regulation of T lymphocyte trafficking into lymph nodes during an immune response by the chemokines macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta. Tedla, N., Wang, H.W., McNeil, H.P., Di Girolamo, N., Hampartzoumian, T., Wakefield, D., Lloyd, A. J. Immunol. (1998) [Pubmed]
  18. Macrophage inflammatory protein 1 modulates macrophage function. Fahey, T.J., Tracey, K.J., Tekamp-Olson, P., Cousens, L.S., Jones, W.G., Shires, G.T., Cerami, A., Sherry, B. J. Immunol. (1992) [Pubmed]
  19. Functional expression of beta-chemokine receptors in osteoblasts: role of regulated upon activation, normal T cell expressed and secreted (RANTES) in osteoblasts and regulation of its secretion by osteoblasts and osteoclasts. Yano, S., Mentaverri, R., Kanuparthi, D., Bandyopadhyay, S., Rivera, A., Brown, E.M., Chattopadhyay, N. Endocrinology (2005) [Pubmed]
  20. An ATF/CREB-binding site is essential for cell-specific and inducible transcription of the murine MIP-1 beta cytokine gene. Proffitt, J., Crabtree, G., Grove, M., Daubersies, P., Bailleul, B., Wright, E., Plumb, M. Gene (1995) [Pubmed]
  21. Purification and biochemical characterization of the D6 chemokine receptor. Blackburn, P.E., Simpson, C.V., Nibbs, R.J., O'Hara, M., Booth, R., Poulos, J., Isaacs, N.W., Graham, G.J. Biochem. J. (2004) [Pubmed]
  22. Altered thymocyte migration during experimental acute Trypanosoma cruzi infection: combined role of fibronectin and the chemokines CXCL12 and CCL4. Mendes-da-Cruz, D.A., Silva, J.S., Cotta-de-Almeida, V., Savino, W. Eur. J. Immunol. (2006) [Pubmed]
  23. Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection. Gonzalez-Juarrero, M., Hattle, J.M., Izzo, A., Junqueira-Kipnis, A.P., Shim, T.S., Trapnell, B.C., Cooper, A.M., Orme, I.M. J. Leukoc. Biol. (2005) [Pubmed]
  24. Naive T cells can mediate delayed-type hypersensitivity response in T cell receptor transgenic mice. Sato, T., Sasahara, T., Nakamura, Y., Osaki, T., Hasegawa, T., Tadakuma, T., Arata, Y., Kumagai, Y., Katsuki, M., Habu, S. Eur. J. Immunol. (1994) [Pubmed]
  25. Immunotoxic effects of carbon tetrachloride--the effect on morphology and function of the immune system in mice. Jírová, D., Sperlingová, I., Halasková, M., Bendová, H., Dabrowská, L. Cent. Eur. J. Public Health (1996) [Pubmed]
  26. Severe Mg-deficiency is not associated with endothelial cell activation in mouse lung. Sabbagh, F., Lecerf, F., Maurois, P., Bac, P., German-Fattal, M. Magnesium research : official organ of the International Society for the Development of Research on Magnesium. (2005) [Pubmed]
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