Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Chemokines: a new class of neuromodulator?

Nature Reviews Neuroscience volume 8, pages 895–903 (2007)Cite this article

Abstract

Chemokines are not only found in the immune system or expressed in inflammatory conditions: they are constitutively present in the brain in both glial cells and neurons. Recently, the possibility has been raised that they might act as neurotransmitters or neuromodulators. Although the evidence is incomplete, emerging data show that chemokines have several of the characteristics that define neurotransmitters. Moreover, their physiological actions resemble those of neuromodulators in the sense that chemokines usually have few effects by themselves in basal conditions, but modify the induced release of neurotransmitters or neuropeptides. These findings, together with the pharmacological development of agonists and antagonists that are selective for chemokine receptors and can cross the blood–brain barrier, open a new era of research in neuroscience.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The neuroanatomical localization of CCL2 and its receptor, CCR2, in the normal adult rat brain.
Figure 2: CCL21 immunoreactivity in presynaptic nerve terminals of cultured mouse cortical neurons.
Figure 3: Colocalization of CCL2 and CCR2 proteins with 'classical' neurotransmitters and with neuropeptides and neurohormones in the adult rat brain.
Figure 4: The modulation by CCL2 of the GABA-induced electrical response on cultured spinal-cord neurons of the adult rat.
Figure 5: The effect of CXCL12 on rat hippocampal neuron morphology.
Figure 6: CXCL12 in the rat substantia nigra induces striatal dopamine release and contralateral circling behaviour.
Figure 7: The different modes of action of neuronal chemokines in the brain.

Similar content being viewed by others

References

  1. Besedovsky, H. O. & del Rey, A. Immune-neuro-endocrine interactions: facts and hypotheses. Endocr. Rev. 17, 64–102 (1996).

    CAS  PubMed  Google Scholar 

  2. Banks, W. A. Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr. Pharm. Des. 11, 973–984 (2005).

    CAS  PubMed  Google Scholar 

  3. Greter, M. et al. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nature Med. 11, 328–334 (2005).

    CAS  PubMed  Google Scholar 

  4. Tambur, A. R. & Roitberg, B. Immunology of the central nervous system. Neurol. Res. 27, 675–678 (2005).

    CAS  PubMed  Google Scholar 

  5. Yoshimura, T. et al. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc. Natl Acad. Sci. USA 84, 9233–9237 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Rossi, D. & Zlotnik, A. The biology of chemokines and their receptors. Annu. Rev. Immunol. 18, 217–242 (2000).

    CAS  PubMed  Google Scholar 

  7. Berger, E. A., Murphy, P. M. & Farber, J. M. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu. Rev. Immunol. 17, 657–700 (1999).

    CAS  PubMed  Google Scholar 

  8. Mennicken, F., Maki, R., de Souza, E. B. & Quirion, R. Chemokines and chemokine receptors in the CNS: a possible role in neuroinflammation and patterning. Trends Pharmacol. Sci. 20, 73–78 (1999).

    CAS  PubMed  Google Scholar 

  9. Ubogu, E. E., Cossoy, M. B. & Ransohoff, R. M. The expression and function of chemokines involved in CNS inflammation. Trends Pharmacol. Sci. 27, 48–55 (2006).

    CAS  PubMed  Google Scholar 

  10. Proudfoot, A. E., Shaw, J. P., Power, C. A. & Wells, T. N. C. in Universes in Delicate Balance: Chemokines and the Nervous System (eds Ransohoff, R. M., Suzuki, K., Proudfoot, A. E. I., Hickey W. F. & Harrison, J. K.) 65–86 (Elsevier, Amsterdam, 2002).

    Google Scholar 

  11. Bajetto, A., Bonavia, R., Barbero, S., Florio, T. & Schettini, G. Chemokines and their receptors in the central nervous system. Front. Neuroendocrinol. 22, 147–184 (2001).

    CAS  PubMed  Google Scholar 

  12. Tran, P. B. & Miller, R. J. Chemokine receptors in the brain: a developing story. J. Comp. Neurol. 457, 1–6 (2003).

    CAS  PubMed  Google Scholar 

  13. Banisadr, G., Rostene, W., Kitabgi, P. & Parsadaniantz, S. M. Chemokines and brain functions. Curr. Drug Targets Inflamm. Allergy 4, 387–399 (2005).

    CAS  PubMed  Google Scholar 

  14. White, F. A., Bhangoo, S. K. & Miller, R. J. Chemokines: integrators of pain and inflammation. Nature Rev. Drug Discov. 4, 834–844 (2005).

    CAS  Google Scholar 

  15. Bacon, K. B. & Harrison, J. K. Chemokines and their receptors in neurobiology: perspectives in physiology and homeostasis. J. Neuroimmunol. 104, 92–97 (2000).

    CAS  PubMed  Google Scholar 

  16. Miller, R. J. & Oh, S. B. in Universes in Delicate Balance: Chemokines and the Nervous System (eds Ransohoff, R. M., Suzuki, K., Proudfoot, A. E. I., Hickey W. F. & Harrison, J. K.) 273–288 (Elsevier, Amsterdam, 2002).

    Google Scholar 

  17. Harrison, J. K. in Universes in Delicate Balance: Chemokines and the Nervous System (eds Ransohoff, R. M., Suzuki, K., Proudfoot, A. E. I., Hickey W. F. & Harrison, J. K.) 237–244 (Elsevier, Amsterdam, 2002).

    Google Scholar 

  18. Mahad, D. J. & Ransohoff, R. M. The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Semin. Immunol. 15, 23–32 (2003).

    CAS  PubMed  Google Scholar 

  19. Fife, B. T., Huffnagle, G. B., Kuziel, W. A. & Karpus, W. J. CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J. Exp. Med. 192, 899–905 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. White, F. A. et al. Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion. Proc. Natl Acad. Sci. USA 102, 14092–14097 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Banisadr, G. et al. Highly regionalized neuronal expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) in rat brain: evidence for its colocalization with neurotransmitters and neuropeptides. J. Comp. Neurol. 489, 275–292 (2005).

    CAS  PubMed  Google Scholar 

  22. Coughlan, C. M. et al. Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons. Neuroscience 97, 591–600 (2000).

    CAS  PubMed  Google Scholar 

  23. Meng, S. Z., Oka, A. & Takashima, S. Developmental expression of monocyte chemoattractant protein-1 in the human cerebellum and brainstem. Brain Dev. 21, 30–35 (1999).

    CAS  PubMed  Google Scholar 

  24. Banisadr, G. et al. Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain: functional effect of MCP-1/CCL2 on calcium mobilization in primary cultured neurons. J. Comp. Neurol. 492, 178–192 (2005).

    CAS  PubMed  Google Scholar 

  25. Gosselin, R. D. et al. Constitutive expression of CCR2 chemokine receptor and inhibition by MCP-1/CCL2 of GABA-induced currents in spinal cord neurones. J. Neurochem. 95, 1023–1034 (2005).

    CAS  PubMed  Google Scholar 

  26. Tham, T. N. et al. Developmental pattern of expression of the alpha chemokine stromal cell-derived factor 1 in the rat central nervous system. Eur. J. Neurosci. 13, 845–856 (2001).

    CAS  PubMed  Google Scholar 

  27. Banisadr, G., Skrzydelski, D., Kitabgi, P., Rostene, W. & Parsadaniantz, S. M. Highly regionalized distribution of stromal cell-derived factor-1/CXCL12 in adult rat brain: constitutive expression in cholinergic, dopaminergic and vasopressinergic neurons. Eur. J. Neurosci. 18, 1593–1606 (2003).

    PubMed  Google Scholar 

  28. Stumm, R. K. et al. A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia. J. Neurosci. 22, 5865–5878 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Xia, M. Q. & Hyman, B. T. Chemokines/chemokine receptors in the central nervous system and Alzheimer's disease. J. Neurovirol. 5, 32–41 (1999).

    CAS  PubMed  Google Scholar 

  30. Harrison, J. K. et al. Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc. Natl Acad. Sci. USA 95, 10896–10901 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Rotsztejn, W., Besson, J., Pattou, E. & Drouva, S. V. Hypothalamic neuropeptides (NP) can be neurotransmitters, neurohormones or neuromodulators. Adv. Physiol. Sci. 14, 217–229 (1981).

    Google Scholar 

  32. de Jong, E. K. et al. Vesicle-mediated transport and release of CCL21 in endangered neurons: a possible explanation for microglia activation remote from a primary lesion. J. Neurosci. 25, 7548–7557 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Callewaere, C. et al. Cellular and subcellular evidence for neuronal interaction between the chemokine SDF-1/CXCL12 and vasopressin: regulation in the hypothalamo-neurohypophysial system of the Brattleboro rats. Endocrinology 27 Sep 2007 (doi: 10.1210/en.2007-1097).

    CAS  PubMed  Google Scholar 

  34. Callewaere, C. et al. The chemokine SDF-1/CXCL12 modulates the firing pattern of vasopressin neurons and counteracts induced vasopressin release through CXCR4. Proc. Natl Acad. Sci. USA 103, 8221–8226 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Baudouin, S. J., Pujol, F., Nicot, A., Kitabgi, P. & Boudin, H. Dendrite-selective redistribution of the chemokine receptor CXCR4 following agonist stimulation. Mol. Cell. Neurosci. 33, 160–169 (2006).

    CAS  PubMed  Google Scholar 

  36. Oh, S. B., Cho, C. & Miller, R. J. Electrophysiological analysis of neuronal chemokine receptors. Methods 29, 335–344 (2003).

    CAS  PubMed  Google Scholar 

  37. Guyon, A., Rovere, C., Cervantes, A., Allaeys, I. & Nahon, J. L. Stromal cell-derived factor-1α directly modulates voltage-dependent currents of the action potential in mammalian neuronal cells. J. Neurochem. 93, 963–973 (2005).

    CAS  PubMed  Google Scholar 

  38. Guyon, A. et al. Complex effects of stromal cell-derived factor-1α on melanin-concentrating hormone neuron excitability. Eur. J. Neurosci. 21, 701–710 (2005).

    CAS  PubMed  Google Scholar 

  39. Guyon, A. et al. Stromal cell-derived factor-1α modulation of the excitability of rat substantia nigra dopaminergic neurones: presynaptic mechanisms. J. Neurochem. 96, 1540–1550 (2006).

    CAS  PubMed  Google Scholar 

  40. Limatola, C. et al. SDF-1α-mediated modulation of synaptic transmission in rat cerebellum. Eur. J. Neurosci. 12, 2497–2504 (2000).

    CAS  PubMed  Google Scholar 

  41. Ragozzino, D., Renzi, M., Giovannelli, A. & Eusebi, F. Stimulation of chemokine CXC receptor 4 induces synaptic depression of evoked parallel fibers inputs onto Purkinje neurons in mouse cerebellum. J. Neuroimmunol. 127, 30–36 (2002).

    CAS  PubMed  Google Scholar 

  42. Oh, S. B., Endoh, T., Simen, A. A., Ren, D. & Miller, R. J. Regulation of calcium currents by chemokines and their receptors. J. Neuroimmunol. 123, 66–75 (2002).

    CAS  PubMed  Google Scholar 

  43. Jazin, E. E., Soderstrom, S., Ebendal, T. & Larhammar, D. Embryonic expression of the mRNA for the rat homologue of the fusin/CXCR-4 HIV-1 co-receptor. J. Neuroimmunol. 79, 148–154 (1997).

    CAS  PubMed  Google Scholar 

  44. McGrath, K. E., Koniski, A. D., Maltby, K. M., McGann, J. K. & Palis, J. Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4. Dev. Biol. 213, 442–456 (1999).

    CAS  PubMed  Google Scholar 

  45. Tissir, F., Wang, C. E. & Goffinet, A. M. Expression of the chemokine receptor Cxcr4 mRNA during mouse brain development. Brain Res. Dev. Brain Res. 149, 63–71 (2004).

    CAS  PubMed  Google Scholar 

  46. Westmoreland, S. V. et al. Developmental expression patterns of CCR5 and CXCR4 in the rhesus macaque brain. J. Neuroimmunol. 122, 146–158 (2002).

    CAS  PubMed  Google Scholar 

  47. Banisadr, G. et al. Neuroanatomical distribution of CXCR4 in adult rat brain and its localization in cholinergic and dopaminergic neurons. Eur. J. Neurosci. 16, 1661–1671 (2002).

    PubMed  Google Scholar 

  48. Stumm, R. K. et al. CXCR4 regulates interneuron migration in the developing neocortex. J. Neurosci. 23, 5123–5130 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Skrzydelski, D. et al. The chemokine stromal cell-derived factor-1/CXCL12 activates the nigrostriatal dopamine system. J. Neurochem. 102, 1175–1183 (2007).

    CAS  PubMed  Google Scholar 

  50. Ludwig, M. et al. Regulation of activity-dependent dendritic vasopressin release from rat supraoptic neurones. J. Physiol. 564, 515–522 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Meucci, O., Fatatis, A., Simen, A. A. & Miller, R. J. Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival. Proc. Natl Acad. Sci. USA 97, 8075–8080 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Goldberg, S. H. et al. CXCR3 expression in human central nervous system diseases. Neuropathol. Appl. Neurobiol. 27, 127–138 (2001).

    CAS  PubMed  Google Scholar 

  53. Horuk, R. et al. Expression of chemokine receptors by subsets of neurons in the central nervous system. J. Immunol. 158, 2882–2890 (1997).

    CAS  PubMed  Google Scholar 

  54. Puma, C., Danik, M., Quirion, R., Ramon, F. & Williams, S. The chemokine interleukin-8 acutely reduces Ca2+ currents in identified cholinergic septal neurons expressing CXCR1 and CXCR2 receptor mRNAs. J. Neurochem. 78, 960–971 (2001).

    CAS  PubMed  Google Scholar 

  55. Streit, W. J., Conde, J. R. & Harrison, J. K. Chemokines and Alzheimer's disease. Neurobiol. Aging 22, 909–913 (2001).

    CAS  PubMed  Google Scholar 

  56. Wells, T. N., Power, C. A. & Proudfoot, A. E. Definition, function and pathophysiological significance of chemokine receptors. Trends Pharmacol. Sci. 19, 376–380 (1998).

    CAS  PubMed  Google Scholar 

  57. Abbadie, C. Chemokines, chemokine receptors and pain. Trends Immunol. 26, 529–534 (2005).

    CAS  PubMed  Google Scholar 

  58. Biber, K., de Jong, E. K., van Weering, H. R. & Boddeke, H. W. Chemokines and their receptors in central nervous system disease. Curr. Drug Targets. 7, 29–46 (2006).

    CAS  PubMed  Google Scholar 

  59. Rogers, T. J., Steele, A. D., Howard, O. M. & Oppenheim, J. J. Bidirectional heterologous desensitization of opioid and chemokine receptors. Ann. NY Acad. Sci. 917, 19–28 (2000).

    CAS  PubMed  Google Scholar 

  60. Szabo, I. et al. Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain. Proc. Natl Acad. Sci. USA 99, 10276–10281 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Zhang, N., Rogers, T. J., Caterina, M. & Oppenheim, J. J. Proinflammatory chemokines, such as C-C chemokine ligand 3, desensitize μ-opioid receptors on dorsal root ganglia neurons. J. Immunol. 173, 594–599 (2004).

    CAS  PubMed  Google Scholar 

  62. Liu, Q. H. et al. HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation. Proc. Natl Acad. Sci. USA 97, 4832–4837 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Liu, Z. et al. Frequency modulation of synchronized Ca2+ spikes in cultured hippocampal networks through G-protein-coupled receptors. J. Neurosci. 23, 4156–4163 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Pujol, F., Kitabgi, P. & Boudin, H. The chemokine SDF-1 differentially regulates axonal elongation and branching in hippocampal neurons. J. Cell Sci. 118, 1071–1080 (2005).

    CAS  PubMed  Google Scholar 

  65. Bajetto, A. et al. Glial and neuronal cells express functional chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor 1. J. Neurochem. 73, 2348–2357 (1999).

    CAS  PubMed  Google Scholar 

  66. Ma, Q. et al. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc. Natl Acad. Sci. USA 95, 9448–9453 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Zhu, Y. et al. Role of the chemokine SDF-1 as the meningeal attractant for embryonic cerebellar neurons. Nature Neurosci. 5, 719–720 (2002).

    CAS  PubMed  Google Scholar 

  68. Lu, M., Grove, E. A. & Miller, R. J. Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc. Natl Acad. Sci. USA 99, 7090–7095 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Tran, P. B., Ren, D., Veldhouse, T. J. & Miller, R. J. Chemokine receptors are expressed widely by embryonic and adult neural progenitor cells. J. Neurosci. Res. 76, 20–34 (2004).

    CAS  PubMed  Google Scholar 

  70. Bagri, A. et al. The chemokine SDF1 regulates migration of dentate granule cells. Development 129, 4249–4260 (2002).

    CAS  PubMed  Google Scholar 

  71. Arakawa, Y. et al. Control of axon elongation via an SDF-1α/Rho/mDia pathway in cultured cerebellar granule neurons. J. Cell Biol. 161, 381–391 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Chalasani, S. H., Sabelko, K. A., Sunshine, M. J., Littman, D. R. & Raper, J. A. A chemokine, SDF-1, reduces the effectiveness of multiple axonal repellents and is required for normal axon pathfinding. J. Neurosci. 23, 1360–1371 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Bolin, L. M. et al. Primary sensory neurons migrate in response to the chemokine RANTES. J. Neuroimmunol. 81, 49–57 (1998).

    CAS  PubMed  Google Scholar 

  74. Belmadani, A. et al. The chemokine stromal cell-derived factor-1 regulates the migration of sensory neuron progenitors. J. Neurosci. 25, 3995–4003 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Lazarini, F., Tham, T. N., Casanova, P., Arenzana-Seisdedos, F. & Dubois-Dalcq, M. Role of the α-chemokine stromal cell-derived factor (SDF-1) in the developing and mature central nervous system. Glia 42, 139–148 (2003).

    PubMed  Google Scholar 

  76. Meucci, O. et al. Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc. Natl Acad. Sci. USA 95, 14500–14505 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Watson, K. & Fan, G. H. Macrophage inflammatory protein 2 inhibits β-amyloid peptide (1–42)-mediated hippocampal neuronal apoptosis through activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. Mol. Pharmacol. 67, 757–765 (2005).

    CAS  PubMed  Google Scholar 

  78. Limatola, C. et al. The chemokine growth-related gene product β protects rat cerebellar granule cells from apoptotic cell death through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors. Proc. Natl Acad. Sci. USA 97, 6197–6201 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Wee, V. W. in Universes in Delicate Balance: Chemokines and the Nervous System (eds Ransohoff, R. M., Suzuki, K., Proudfoot, A. E. I., Hickey W. F. & Harrison, J. K.) 151–158 (Elsevier, Amsterdam, 2002).

    Google Scholar 

  80. Vergote, D. et al. Proteolytic processing of SDF-1α reveals a change in receptor specificity mediating HIV-associated neurodegeneration. Proc. Natl Acad. Sci. USA 103, 19182–19187 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Boudin, H., Pelaprat, D., Rostene, W., Pickel, V. M. & Beaudet, A. Correlative ultrastructural distribution of neurotensin receptor proteins and binding sites in the rat substantia nigra. J. Neurosci. 18, 8473–8484 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Agnati, L. F. et al. Volume transmission and wiring transmission from cellular to molecular networks: history and perspectives. Acta Physiol. 187, 329–344 (2006).

    CAS  Google Scholar 

  83. Sakamoto, Y. et al. Endotoxin activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system. Endocrinology 137, 4503–4506 (1996).

    CAS  PubMed  Google Scholar 

  84. Florio, T. et al. Chemokine stromal cell-derived factor 1α induces proliferation and growth hormone release in GH4C1 rat pituitary adenoma cell line through multiple intracellular signals. Mol. Pharmacol. 69, 539–546 (2006).

    CAS  PubMed  Google Scholar 

  85. Rostene, W. & Buckingham, J. C. Chemokines as modulators of neuroendocrine functions. J. Mol. Endocrinol. 38, 351–353 (2007).

    CAS  PubMed  Google Scholar 

  86. Guyon, A. & Nahon, J. L. Multiple actions of the chemokine stromal cell-derived factor-1α on neuronal activity. J. Mol. Endocrinol. 38, 365–376 (2007).

    CAS  PubMed  Google Scholar 

  87. Barbieri, F. et al. Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function. J. Mol. Endocrinol. 38, 383–389 (2007).

    CAS  PubMed  Google Scholar 

  88. Callewaere, C., Banisadr, G., Rostene, W. & Parsadaniantz, S. M. Chemokines and chemokine receptors in the brain: implication in neuroendocrine regulation. J. Mol. Endocrinol. 38, 355–363 (2007).

    CAS  PubMed  Google Scholar 

  89. Tanaka, T., Minami, M., Nakagawa, T. & Satoh, M. Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain. Neurosci. Res. 48, 463–469 (2004).

    CAS  PubMed  Google Scholar 

  90. Abbadie, C. et al. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc. Natl Acad. Sci. USA 100, 7947–7952 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Giovannelli, A. et al. CXC chemokines interleukin-8 (IL-8) and growth-related gene product α (GROα) modulate Purkinje neuron activity in mouse cerebellum. J. Neuroimmunol. 92, 122–132 (1998).

    CAS  PubMed  Google Scholar 

  92. Betancur, C., Azzi, M. & Rostene, W. Nonpeptide antagonists of neuropeptide receptors: tools for research and therapy. Trends Pharmacol. Sci. 18, 372–386 (1997).

    CAS  PubMed  Google Scholar 

  93. Brodmerkel, C. M. et al. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J. Immunol. 175, 5370–5378 (2005).

    CAS  PubMed  Google Scholar 

  94. Zhang, Y., Ernst, C. A. & Rollins, B. J. MCP-1: structure/activity analysis. Methods 10, 93–103 (1996).

    CAS  PubMed  Google Scholar 

  95. Crump, M. P. et al. Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1. EMBO J. 16, 6996–7007 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Ransohoff, R. M., Sukuzi, K., Proudfoot, A. E., Hickey, W. F. & Harrison, JK. (eds) Universes in Delicate Balance: Chemokines and the Nervous System 1–387 (Elsevier, Amsterdam, 2002).

    Google Scholar 

Download references

Acknowledgements

Many thanks to G. Banisadr, C. Callewaere, R. Gosselin and D. Skrzydelski, and several of our collaborators, for the data they brought in the laboratory, which allowed us to support some of the hypotheses raised in this paper.

Author information

Authors and Affiliations

  1. William Rostène, Patrick Kitabgi and Stéphane Mélik Parsadaniantz are all at INSERM-UPMC 732, Hôpital St Antoine, 184 Rue du Fg St Antoine, 75012 Paris, France.,

    William Rostène, Patrick Kitabgi & Stéphane Mélik Parsadaniantz

Authors
  1. William Rostène
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick Kitabgi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stéphane Mélik Parsadaniantz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William Rostène.

Related links

Related links

FURTHER INFORMATION

Cytokine family database

GPCRDB: information system for G protein-coupled receptors

United States Patent and Trademark Office

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rostène, W., Kitabgi, P. & Parsadaniantz, S. Chemokines: a new class of neuromodulator?. Nat Rev Neurosci 8, 895–903 (2007). https://doi.org/10.1038/nrn2255

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2255

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing