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Gene Review

Ccl2  -  chemokine (C-C motif) ligand 2

Mus musculus

Synonyms: AI323594, C-C motif chemokine 2, HC11, JE, Je, ...
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Disease relevance of Ccl2


Psychiatry related information on Ccl2

  • To assess the role of CCL2/MCP-1 in opiate drug abuse and HIV-1 comorbidity, the effects of systemic morphine and intrastriatal HIV-1 Tat on macrophage/microglial and astroglial activation were assessed in wild type and CCR2 null mice [6].

High impact information on Ccl2


Chemical compound and disease context of Ccl2


Biological context of Ccl2


Anatomical context of Ccl2


Associations of Ccl2 with chemical compounds

  • IgG and NADPH increased the transcription rates for JE/MCP-1 and CSF-1, effects inhibited by TMTU [17].
  • Sodium salicylate attenuates the levels of MCP-1/JE and IP-10 mRNA in a concentration- and time-dependent manner [18].
  • In the present studies, we used CCR2 knockout (CCR2-/-) mice to examine the role of MCP-1 in acetaminophen-induced macrophage accumulation in the liver, expression of inflammatory cytokines, and hepatotoxicity [19].
  • In the present study, we examined the effect of retinoic acid (RA) on the cytokine-induced JE/MCP-1 expression in the cells [20].
  • In normal mice, instillation of MCP-1 induced prolonged airway hyperreactivity and histamine release [11].
  • Besides biogenic process, microtubules control LTB4-synthesizing function of MCP-1-elicited lipid bodies, in part by regulating the compartmentalization of key proteins, as adipose differentiation-related protein and 5-lipoxygenase [21].

Physical interactions of Ccl2

  • Evidence that MCP-1 levels are regulated by receptor binding and internalization was suggested by its rapid decline when added to WT macrophages at 37 degrees C but not 4 degrees C. These studies indicate that CCR2 plays an important role in regulating T cell responses and controlling the level of MCP-1 at inflammatory sites [22].
  • U-0126 also inhibited an increase in nuclear factor-kappaB and activator protein-1 DNA-binding activity of MCP-1 promoter by protein overload in mProx cells [23].
  • The biological effects of monocyte chemoattractant protein (MCP) 1 are mediated by binding to C-C chemokine receptor (CCR) 2 [19].
  • Sp1 binding is critical for promoter assembly and activation of the MCP-1 gene by tumor necrosis factor [24].

Regulatory relationships of Ccl2


Other interactions of Ccl2


Analytical, diagnostic and therapeutic context of Ccl2


  1. Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice. Chow, F.Y., Nikolic-Paterson, D.J., Ma, F.Y., Ozols, E., Rollins, B.J., Tesch, G.H. Diabetologia (2007) [Pubmed]
  2. An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Ambati, J., Anand, A., Fernandez, S., Sakurai, E., Lynn, B.C., Kuziel, W.A., Rollins, B.J., Ambati, B.K. Nat. Med. (2003) [Pubmed]
  3. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Gu, L., Okada, Y., Clinton, S.K., Gerard, C., Sukhova, G.K., Libby, P., Rollins, B.J. Mol. Cell (1998) [Pubmed]
  4. Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. Huang, D.R., Wang, J., Kivisakk, P., Rollins, B.J., Ransohoff, R.M. J. Exp. Med. (2001) [Pubmed]
  5. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. Lu, B., Rutledge, B.J., Gu, L., Fiorillo, J., Lukacs, N.W., Kunkel, S.L., North, R., Gerard, C., Rollins, B.J. J. Exp. Med. (1998) [Pubmed]
  6. CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates. El-Hage, N., Wu, G., Ambati, J., Bruce-Keller, A.J., Knapp, P.E., Hauser, K.F. J. Neuroimmunol. (2006) [Pubmed]
  7. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cochran, B.H., Reffel, A.C., Stiles, C.D. Cell (1983) [Pubmed]
  8. Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Wyss-Coray, T., Loike, J.D., Brionne, T.C., Lu, E., Anankov, R., Yan, F., Silverstein, S.C., Husemann, J. Nat. Med. (2003) [Pubmed]
  9. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Gu, L., Tseng, S., Horner, R.M., Tam, C., Loda, M., Rollins, B.J. Nature (2000) [Pubmed]
  10. Role of monocyte chemotactic protein-1/CC chemokine ligand 2 on gamma delta T lymphocyte trafficking during inflammation induced by lipopolysaccharide or Mycobacterium bovis bacille Calmette-Guérin. Penido, C., Vieira-de-Abreu, A., Bozza, M.T., Castro-Faria-Neto, H.C., Bozza, P.T. J. Immunol. (2003) [Pubmed]
  11. Monocyte chemoattractant protein-1 mediates cockroach allergen-induced bronchial hyperreactivity in normal but not CCR2-/- mice: the role of mast cells. Campbell, E.M., Charo, I.F., Kunkel, S.L., Strieter, R.M., Boring, L., Gosling, J., Lukacs, N.W. J. Immunol. (1999) [Pubmed]
  12. Early signal transduction by the receptor to the chemokine monocyte chemotactic protein-1 in a murine T cell hybrid. Dubois, P.M., Palmer, D., Webb, M.L., Ledbetter, J.A., Shapiro, R.A. J. Immunol. (1996) [Pubmed]
  13. Endogenous monocyte chemoattractant protein-1 (MCP-1) protects mice in a model of acute septic peritonitis: cross-talk between MCP-1 and leukotriene B4. Matsukawa, A., Hogaboam, C.M., Lukacs, N.W., Lincoln, P.M., Strieter, R.M., Kunkel, S.L. J. Immunol. (1999) [Pubmed]
  14. Perturbation of chemokine networks by gene deletion alters the reinforcing actions of ethanol. Blednov, Y.A., Bergeson, S.E., Walker, D., Ferreira, V.M., Kuziel, W.A., Harris, R.A. Behav. Brain Res. (2005) [Pubmed]
  15. Induction of monocyte- and T-cell-attracting chemokines in the lung during the generation of idiopathic pneumonia syndrome following allogeneic murine bone marrow transplantation. Panoskaltsis-Mortari, A., Strieter, R.M., Hermanson, J.R., Fegeding, K.V., Murphy, W.J., Farrell, C.L., Lacey, D.L., Blazar, B.R. Blood (2000) [Pubmed]
  16. Tumor necrosis factor-alpha induces expression of monocyte chemoattractant JE via fos and jun genes in clonal osteoblastic MC3T3-E1 cells. Hanazawa, S., Takeshita, A., Amano, S., Semba, T., Nirazuka, T., Katoh, H., Kitano, S. J. Biol. Chem. (1993) [Pubmed]
  17. Oxygen radicals as second messengers for expression of the monocyte chemoattractant protein, JE/MCP-1, and the monocyte colony-stimulating factor, CSF-1, in response to tumor necrosis factor-alpha and immunoglobulin G. Evidence for involvement of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase. Satriano, J.A., Shuldiner, M., Hora, K., Xing, Y., Shan, Z., Schlondorff, D. J. Clin. Invest. (1993) [Pubmed]
  18. Chemokine gene expression in bone marrow stromal cells: downregulation with sodium salicylate. Gautam, S.C., Pindolia, K.R., Noth, C.J., Janakiraman, N., Xu, Y.X., Chapman, R.A. Blood (1995) [Pubmed]
  19. Role of CCR2 in macrophage migration into the liver during acetaminophen-induced hepatotoxicity in the mouse. Dambach, D.M., Watson, L.M., Gray, K.R., Durham, S.K., Laskin, D.L. Hepatology (2002) [Pubmed]
  20. Retinoic acid suppression of c-fos gene inhibits expression of tumor necrosis factor-alpha-induced monocyte chemoattractant JE/MCP-1 in clonal osteoblastic MC3T3-E1 cells. Hanazawa, S., Takeshita, A., Kitano, S. J. Biol. Chem. (1994) [Pubmed]
  21. Monocyte chemoattractant protein-1/CC chemokine ligand 2 controls microtubule-driven biogenesis and leukotriene B4-synthesizing function of macrophage lipid bodies elicited by innate immune response. Pacheco, P., Vieira-de-Abreu, A., Gomes, R.N., Barbosa-Lima, G., Wermelinger, L.B., Maya-Monteiro, C.M., Silva, A.R., Bozza, M.T., Castro-Faria-Neto, H.C., Bandeira-Melo, C., Bozza, P.T. J. Immunol. (2007) [Pubmed]
  22. Ccr2 regulates the level of MCP-1/CCL2 in vitro and at inflammatory sites and controls T cell activation in response to alloantigen. Tylaska, L.A., Boring, L., Weng, W., Aiello, R., Charo, I.F., Rollins, B.J., Gladue, R.P. Cytokine (2002) [Pubmed]
  23. Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells. Takaya, K., Koya, D., Isono, M., Sugimoto, T., Sugaya, T., Kashiwagi, A., Haneda, M. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  24. Sp1 binding is critical for promoter assembly and activation of the MCP-1 gene by tumor necrosis factor. Ping, D., Boekhoudt, G., Zhang, F., Morris, A., Philipsen, S., Warren, S.T., Boss, J.M. J. Biol. Chem. (2000) [Pubmed]
  25. Regulatory effects of iNOS on acute lung inflammatory responses in mice. Speyer, C.L., Neff, T.A., Warner, R.L., Guo, R.F., Sarma, J.V., Riedemann, N.C., Murphy, M.E., Murphy, H.S., Ward, P.A. Am. J. Pathol. (2003) [Pubmed]
  26. IL-18 induces monocyte chemotactic protein-1 production in macrophages through the phosphatidylinositol 3-kinase/Akt and MEK/ERK1/2 pathways. Yoo, J.K., Kwon, H., Khil, L.Y., Zhang, L., Jun, H.S., Yoon, J.W. J. Immunol. (2005) [Pubmed]
  27. MCP-1 is up-regulated in unstressed and stressed HO-1 knockout mice: Pathophysiologic correlates. Pittock, S.T., Norby, S.M., Grande, J.P., Croatt, A.J., Bren, G.D., Badley, A.D., Caplice, N.M., Griffin, M.D., Nath, K.A. Kidney Int. (2005) [Pubmed]
  28. Negative regulation of monocyte chemoattractant protein-1 gene expression by a mouse estrogen-enhanced transcript. Xie, L.P., Fu, W.X., Jin, C., Dong, X.Y., Chen, W.F. Eur. J. Immunol. (2002) [Pubmed]
  29. Novel chemokine responsiveness and mobilization of neutrophils during sepsis. Speyer, C.L., Gao, H., Rancilio, N.J., Neff, T.A., Huffnagle, G.B., Sarma, J.V., Ward, P.A. Am. J. Pathol. (2004) [Pubmed]
  30. Monocyte chemoattractant protein-1 synthesis by murine lung fibroblasts modulates CD4+ T cell activation. Hogaboam, C.M., Lukacs, N.W., Chensue, S.W., Strieter, R.M., Kunkel, S.L. J. Immunol. (1998) [Pubmed]
  31. Susceptibility to experimental Lyme arthritis correlates with KC and monocyte chemoattractant protein-1 production in joints and requires neutrophil recruitment via CXCR2. Brown, C.R., Blaho, V.A., Loiacono, C.M. J. Immunol. (2003) [Pubmed]
  32. Hydrogen peroxide induces murine macrophage chemokine gene transcription via extracellular signal-regulated kinase- and cyclic adenosine 5'-monophosphate (cAMP)-dependent pathways: involvement of NF-kappa B, activator protein 1, and cAMP response element binding protein. Jaramillo, M., Olivier, M. J. Immunol. (2002) [Pubmed]
  33. Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Kuziel, W.A., Morgan, S.J., Dawson, T.C., Griffin, S., Smithies, O., Ley, K., Maeda, N. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  34. A critical role for CCR2/MCP-1 interactions in the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation. Hildebrandt, G.C., Duffner, U.A., Olkiewicz, K.M., Corrion, L.A., Willmarth, N.E., Williams, D.L., Clouthier, S.G., Hogaboam, C.M., Reddy, P.R., Moore, B.B., Kuziel, W.A., Liu, C., Yanik, G., Cooke, K.R. Blood (2004) [Pubmed]
  35. Experimental autoimmune encephalomyelitis on the SJL mouse: effect of gamma delta T cell depletion on chemokine and chemokine receptor expression in the central nervous system. Rajan, A.J., Asensio, V.C., Campbell, I.L., Brosnan, C.F. J. Immunol. (2000) [Pubmed]
  36. Blocking the monocyte chemoattractant protein-1/CCR2 chemokine pathway induces permanent survival of islet allografts through a programmed death-1 ligand-1-dependent mechanism. Lee, I., Wang, L., Wells, A.D., Ye, Q., Han, R., Dorf, M.E., Kuziel, W.A., Rollins, B.J., Chen, L., Hancock, W.W. J. Immunol. (2003) [Pubmed]
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