Chemokines

Chemokines have been defined as small cytokines involved in the migration and activation of cells, such as lymphocytes and phagocytic cells, and playing a central role in inflammation1. The term itself is a combination of chemotaxis and cytokine. Chemokines work through a large family of G protein-coupled receptors. Chemokines are classified in families (CXC, C, CX3C, and CC), with the ligands named with an ‘L’ and the receptors named with an ‘R’. For example, IL-8 is classified as CXCL8, and its receptors are CXCR1 and CXCR22. In addition to their role in inflammation, chemokines are major regulators of malignancy and are produced by tumor cells3, with all cells likely able to produce them under certain conditions4.

Chemokines are redundant in their action on target cells, and chemokine/receptor interactions are promiscuous, with receptors interacting with multiple ligands4. CCL-11 (eotaxin) interacts with the CCR3 receptor2 and is elevated in the serum of patients with inflammatory bowel disease5. CXCL1 (Gro-α) binds to CXCR1 and CXCR2 and is a potential urinary biomarker of kidney damage6. CCL1 (I-309) binds to CCR82 and is a cerebrospinal fluid biomarker correlating with the severity of cognitive impairment in Alzheimer’s patients7. Its murine equivalent is CCL1 (TCA3) and CCL22 (MDC). CXCL8 (IL-8) is a human chemokine that binds to CXCR1 and CXCR2; murine protein CXCL1 (KC) is a close equivalent2. CXCL8 is a well-known proinflammatory and atherogenic protein8,9.

CXCL10 (IP-10) is one of many chemokines that activates the CXCR3 receptor2, with protein levels being indicative of responses to treatment of hepatitis C infection10. CCL2 (MCP-1) interacts with CCR22 and has been studied as a biomarker in a variety of illnesses, from chronic obstructive pulmonary disease11 to schizophrenia12. CCL5 (RANTES) activates many CCR receptors2 and is postulated to promote angiogenesis and metastasis13. CCL17 (TARC) interacts with CCR42 and is involved in Hodgkin’s lymphoma14. CXCL12 (SDF-1) activates CXCR42 and contributes to cancer metastasis15.

As these examples demonstrate, chemokines already are useful biomarkers for many diseases. Panels and profiles of chemokines in addition to other proteins will greatly expand the suitability of chemokines as biomarkers.

 

Serum Markers

Eotaxin, Gro-α, I-309, IL-8, IP-10, MCP-1, MCP-2, RANTES, TARC, KC, MDC, SDF-1, TCA-3

 

Chemokines Markers in Q-Plex™ Kits

References

  1. Janeway C, Travers P: Immunobiology : the immune system in health and disease. London ; San Francisco New York: Current Biology Limited ;Garland Pub. Inc.; 1994.
  2. Bacon K, Baggiolini M, Broxmeyer H, Horuk R, Lindley I, Mantovani A, Matsushima K, Murphy P, Nomiyama H, Oppenheim J, et al: Chemokine/chemokine receptor nomenclature. J Leukoc Biol 2001, 70:465-466.
  3. Handel TM, Hamel DJ: Chemokines. 1st edn. Amsterdam ; Boston: Elsevier/Academic Press; 2009.
    Mantovani A: Chemokines. Basel ; New York: Karger; 1999.
  4. Mantovani A: Chemokines. Basel ; New York: Karger; 1999.
  5. Mir A, Minguez M, Tatay J, Pascual I, Pena A, Sanchiz V, Almela P, Mora F, Benages A: Elevated serum eotaxin levels in patients with inflammatory bowel disease. Am J Gastroenterol 2002, 97:1452-1457.
  6. Lisowska-Myjak B: Serum and urinary biomarkers of acute kidney injury. Blood Purif 2010, 29:357-365.
  7. Hu WT, Chen-Plotkin A, Arnold SE, Grossman M, Clark CM, Shaw LM, Pickering E, Kuhn M, Chen Y, McCluskey L, et al: Novel CSF biomarkers for Alzheimer’s disease and mild cognitive impairment. Acta Neuropathol 2010, 119:669-678.
  8. Zheng L, Martins-Green M: Molecular mechanisms of thrombin-induced interleukin-8 (IL-8/CXCL8) expression in THP-1-derived and primary human macrophages. J Leukoc Biol 2007, 82:619-629.
  9. Luppi F, Longo AM, de Boer WI, Rabe KF, Hiemstra PS: Interleukin-8 stimulates cell proliferation in non-small cell lung cancer through epidermal growth factor receptor transactivation. Lung Cancer 2007, 56:25-33.
  10. Romero AI, Lagging M, Westin J, Dhillon AP, Dustin LB, Pawlotsky JM, Neumann AU, Ferrari C, Missale G, Haagmans BL, et al: Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection. J Infect Dis 2006, 194:895-903.
  11. de Torres JP, Casanova C, Pinto-Plata V, Varo N, Restituto P, Cordoba-Lanus E, Baz-Davila R, Aguirre-Jaime A, Celli BR: Gender Differences in Plasma Biomarker Levels in a Cohort of COPD Patients: A Pilot Study. PLoS One 2011, 6:e16021.
  12. Reale M, Patruno A, De Lutiis MA, Pesce M, Felaco M, Di Giannantonio M, Di Nicola M, Grilli A: Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls. BMC Neurosci 2011, 12:13.
  13. Levy JA: The unexpected pleiotropic activities of RANTES. J Immunol 2009, 182:3945-3946.
  14. Maggio E, van den Berg A, Diepstra A, Kluiver J, Visser L, Poppema S: Chemokines, cytokines and their receptors in Hodgkin’s lymphoma cell lines and tissues. Ann Oncol 2002, 13 Suppl 1:52-56.
  15. Huang F, Geng XP: Chemokines and hepatocellular carcinoma. World J Gastroenterol 2010, 16:1832-1836.

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