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Gene Review

CXCL10  -  chemokine (C-X-C motif) ligand 10

Homo sapiens

Synonyms: 10 kDa interferon gamma-induced protein, C-X-C motif chemokine 10, C7, Gamma-IP10, IFI10, ...
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Disease relevance of CXCL10


Psychiatry related information on CXCL10


High impact information on CXCL10

  • In parallel, they show reduced expression of proinflammatory chemokines and cytokines, such as CXCL10, CCL2, and transforming growth factor-beta2, and of chondroitin sulfate proteoglycans participating in the formation of the glial scar [8].
  • An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4 [9].
  • In addition, higher potency and efficacy of I-TAC over IP-10 and HuMig is demonstrated by transient mobilization of intracellular calcium as well as chemotactic migration in both activated T cells and transfected cell lines expressing CXCR3 [10].
  • IP-10 protein was detected in keratinocytes and the dermal infiltrate from active psoriatic plaques using an affinity-purified rabbit anti-IP-10 antibody in immunoperoxidase studies [11].
  • Gene expression profiling revealed that the 3 oncogenes activate a common transcriptional program in thyroid cells that includes upregulation of the CXCL1 and CXCL10 chemokines, which in turn stimulate proliferation and invasion [12].

Chemical compound and disease context of CXCL10


Biological context of CXCL10


Anatomical context of CXCL10


Associations of CXCL10 with chemical compounds

  • These results suggest that plasma concentrations of immunoreactive CXCL10 may be a predictor of responsiveness or nonresponsiveness to antiviral therapy with pegylated interferon (IFN) with or without ribavirin [25].
  • IP-10/CXCL10 bursts, which were not observed in glatiramer acetate (GA)-treated patients, correlated with occurrence of flu-like symptoms [26].
  • CXCL10-induced up-regulation of CXCR3 expression in the three cell lines was inhibited by cycloheximide, indicating that de novo protein synthesis is required for this process [27].
  • The CSF concentration of CXCL10 was positively correlated with the CSF leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis [13].
  • Of interest, intracellular [Ca(2+)] did not rise in response to I-TAC, IP-10, or Mig [28].

Physical interactions of CXCL10

  • Complete deletion of the C-tail, including Hx8, resulted in an inactive phenotype that lacks CXCL8 binding sites and has an increased number of binding sites for CXCL10 [29].
  • Chromatin imunoprecipitation combined with real-time PCR was used to check acetylation of histone H4 and recruitment of the STAT1 complex to the ISRE locus of the CXCL10 gene [30].

Regulatory relationships of CXCL10

  • Furthermore, the presence of CCL5 and CXCL10 in the cytolytic granules of tissue-infiltrating CD8(+) T cells expressing CCR5 and CXCR3 reveals a potential self-recruiting mechanism involving activated effector cytotoxic T cells [31].
  • CXCR3 expression was significantly induced by the overexpression of CXCL10 as determined by RT-PCR and FACS [32].
  • Interestingly, the synthesis of CXCL10 was mainly dependent on the Mtb-induced production of IFN-alpha beta [2].
  • CXCL10 production from cytomegalovirus-stimulated microglia is regulated by both human and viral interleukin-10 [33].
  • Finally, adenosine augmented the release of the chemokine CCL17 and inhibited CXCL10 production by mDCs [34].

Other interactions of CXCL10

  • Elevations in CXC ligand 9 (CXCL9), CXCL10, and CXCL11 were observed in all patients with HCV [25].
  • Finally, we observed intense expression of CXCL10 and CXCR3 in association with human breast cancer in situ, indicating that these observations may be of pathophysiologic significance [1].
  • The combination of CCL5 with CXCL10 but not the other chemokines markedly increased recruitment [35].
  • Migration was subsequently inhibited by addition of neutralizing antibody to CCL4 and CXCL10 [36].
  • Bacteria-induced CCL2, CCL7, CXCL9, and CXCL10 mRNA expression was partially dependent on ongoing protein synthesis [37].

Analytical, diagnostic and therapeutic context of CXCL10


  1. Ras-induced Modulation of CXCL10 and Its Receptor Splice Variant CXCR3-B in MDA-MB-435 and MCF-7 Cells: Relevance for the Development of Human Breast Cancer. Datta, D., Flaxenburg, J.A., Laxmanan, S., Geehan, C., Grimm, M., Waaga-Gasser, A.M., Briscoe, D.M., Pal, S. Cancer Res. (2006) [Pubmed]
  2. IFN-alpha beta released by Mycobacterium tuberculosis-infected human dendritic cells induces the expression of CXCL10: selective recruitment of NK and activated T cells. Lande, R., Giacomini, E., Grassi, T., Remoli, M.E., Iona, E., Miettinen, M., Julkunen, I., Coccia, E.M. J. Immunol. (2003) [Pubmed]
  3. Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with Sjögren's syndrome. Ogawa, N., Ping, L., Zhenjun, L., Takada, Y., Sugai, S. Arthritis Rheum. (2002) [Pubmed]
  4. Serum concentrations of the interferon-gamma-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease. Nicoletti, F., Conget, I., Di Mauro, M., Di Marco, R., Mazzarino, M.C., Bendtzen, K., Messina, A., Gomis, R. Diabetologia (2002) [Pubmed]
  5. Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation. Harvey, C.E., Post, J.J., Palladinetti, P., Freeman, A.J., Ffrench, R.A., Kumar, R.K., Marinos, G., Lloyd, A.R. J. Leukoc. Biol. (2003) [Pubmed]
  6. Neuronal apoptosis is mediated by CXCL10 overexpression in simian human immunodeficiency virus encephalitis. Sui, Y., Potula, R., Dhillon, N., Pinson, D., Li, S., Nath, A., Anderson, C., Turchan, J., Kolson, D., Narayan, O., Buch, S. Am. J. Pathol. (2004) [Pubmed]
  7. Candidate gene analysis of IP-10 gene in patients with Alzheimer's disease. Venturelli, E., Galimberti, D., Fenoglio, C., Lovati, C., Finazzi, D., Guidi, I., Corrà, B., Scalabrini, D., Clerici, F., Mariani, C., Forloni, G., Bresolin, N., Scarpini, E. Neurosci. Lett. (2006) [Pubmed]
  8. Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. Brambilla, R., Bracchi-Ricard, V., Hu, W.H., Frydel, B., Bramwell, A., Karmally, S., Green, E.J., Bethea, J.R. J. Exp. Med. (2005) [Pubmed]
  9. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. Lasagni, L., Francalanci, M., Annunziato, F., Lazzeri, E., Giannini, S., Cosmi, L., Sagrinati, C., Mazzinghi, B., Orlando, C., Maggi, E., Marra, F., Romagnani, S., Serio, M., Romagnani, P. J. Exp. Med. (2003) [Pubmed]
  10. Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. Cole, K.E., Strick, C.A., Paradis, T.J., Ogborne, K.T., Loetscher, M., Gladue, R.P., Lin, W., Boyd, J.G., Moser, B., Wood, D.E., Sahagan, B.G., Neote, K. J. Exp. Med. (1998) [Pubmed]
  11. Detection of a gamma interferon-induced protein IP-10 in psoriatic plaques. Gottlieb, A.B., Luster, A.D., Posnett, D.N., Carter, D.M. J. Exp. Med. (1988) [Pubmed]
  12. The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. Melillo, R.M., Castellone, M.D., Guarino, V., De Falco, V., Cirafici, A.M., Salvatore, G., Caiazzo, F., Basolo, F., Giannini, R., Kruhoffer, M., Orntoft, T., Fusco, A., Santoro, M. J. Clin. Invest. (2005) [Pubmed]
  13. Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis. Sørensen, T.L., Sellebjerg, F., Jensen, C.V., Strieter, R.M., Ransohoff, R.M. Eur. J. Neurol. (2001) [Pubmed]
  14. Chemokines in health and disease. Gangur, V., Birmingham, N.P., Thanesvorakul, S. Vet. Immunol. Immunopathol. (2002) [Pubmed]
  15. Elevated serum levels of CXCL9/monokine induced by interferon-gamma and CXCL10/interferon-gamma-inducible protein-10 in ocular sarcoidosis. Takeuchi, M., Oh-I, K., Suzuki, J., Hattori, T., Takeuchi, A., Okunuki, Y., Usui, Y., Usui, M. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  16. Akt/protein kinase B activation by adenovirus vectors contributes to NFkappaB-dependent CXCL10 expression. Liu, Q., White, L.R., Clark, S.A., Heffner, D.J., Winston, B.W., Tibbles, L.A., Muruve, D.A. J. Virol. (2005) [Pubmed]
  17. Serum levels of the interferon-gamma-inducible alpha chemokine CXCL10 in patients with active Graves' disease, and modulation by methimazole therapy and thyroidectomy. Antonelli, A., Fallahi, P., Rotondi, M., Ferrari, S.M., Serio, M., Miccoli, P. The British journal of surgery. (2006) [Pubmed]
  18. Iodine-131 given for therapeutic purposes modulates differently interferon-gamma-inducible alpha-chemokine CXCL10 serum levels in patients with active Graves' disease or toxic nodular goiter. Antonelli, A., Rotondi, M., Fallahi, P., Grosso, M., Boni, G., Ferrari, S.M., Romagnani, P., Serio, M., Mariani, G., Ferrannini, E. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  19. A functional IFN-gamma-inducible protein-10/CXCL10-specific receptor expressed by epithelial and endothelial cells that is neither CXCR3 nor glycosaminoglycan. Soejima, K., Rollins, B.J. J. Immunol. (2001) [Pubmed]
  20. Immunohistochemical evidence of a cytokine and chemokine network in three patients with Erdheim-Chester disease: Implications for pathogenesis. Stoppacciaro, A., Ferrarini, M., Salmaggi, C., Colarossi, C., Praderio, L., Tresoldi, M., Beretta, A.A., Sabbadini, M.G. Arthritis Rheum. (2006) [Pubmed]
  21. CCL22-induced responses are powerfully enhanced by synergy inducing chemokines via CCR4: evidence for the involvement of first beta-strand of chemokine. Sebastiani, S., Danelon, G., Gerber, B., Uguccioni, M. Eur. J. Immunol. (2005) [Pubmed]
  22. Roles for CXC chemokine ligands 10 and 11 in recruiting CD4+ T cells to HIV-1-infected monocyte-derived macrophages, dendritic cells, and lymph nodes. Foley, J.F., Yu, C.R., Solow, R., Yacobucci, M., Peden, K.W., Farber, J.M. J. Immunol. (2005) [Pubmed]
  23. Compartment-specific expression and function of the chemokine IP-10/CXCL10 in a model of renal endothelial microvascular injury. Panzer, U., Steinmetz, O.M., Reinking, R.R., Meyer, T.N., Fehr, S., Schneider, A., Zahner, G., Wolf, G., Helmchen, U., Schaerli, P., Stahl, R.A., Thaiss, F. J. Am. Soc. Nephrol. (2006) [Pubmed]
  24. Cell surface heparan sulfate participates in CXCL1-induced signaling. Wang, D., Sai, J., Richmond, A. Biochemistry (2003) [Pubmed]
  25. Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C. Butera, D., Marukian, S., Iwamaye, A.E., Hembrador, E., Chambers, T.J., Di Bisceglie, A.M., Charles, E.D., Talal, A.H., Jacobson, I.M., Rice, C.M., Dustin, L.B. Blood (2005) [Pubmed]
  26. Interferon-beta induces transient systemic IP-10/CXCL10 chemokine release in patients with multiple sclerosis. Buttmann, M., Merzyn, C., Rieckmann, P. J. Neuroimmunol. (2004) [Pubmed]
  27. The expression of the chemokine receptor CXCR3 and its ligand, CXCL10, in human breast adenocarcinoma cell lines. Goldberg-Bittman, L., Neumark, E., Sagi-Assif, O., Azenshtein, E., Meshel, T., Witz, I.P., Ben-Baruch, A. Immunol. Lett. (2004) [Pubmed]
  28. CXCR3 chemokine receptor-induced chemotaxis in human airway epithelial cells: role of p38 MAPK and PI3K signaling pathways. Shahabuddin, S., Ji, R., Wang, P., Brailoiu, E., Dun, N., Yang, Y., Aksoy, M.O., Kelsen, S.G. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  29. Helix 8 of the Viral Chemokine Receptor ORF74 Directs Chemokine Binding. Verzijl, D., Pardo, L., van Dijk, M., Gruijthuijsen, Y.K., Jongejan, A., Timmerman, H., Nicholas, J., Schwarz, M., Murphy, P.M., Leurs, R., Smit, M.J. J. Biol. Chem. (2006) [Pubmed]
  30. Histone Deacetylation Is Involved in Activation of CXCL10 Upon IFNgamma Stimulation. Guo, J.J., Li, Q.I., Zhang, J., Huang, A.L. Mol. Cells (2006) [Pubmed]
  31. Infiltrating CD8+ T cells in oral lichen planus predominantly express CCR5 and CXCR3 and carry respective chemokine ligands RANTES/CCL5 and IP-10/CXCL10 in their cytolytic granules: a potential self-recruiting mechanism. Iijima, W., Ohtani, H., Nakayama, T., Sugawara, Y., Sato, E., Nagura, H., Yoshie, O., Sasano, T. Am. J. Pathol. (2003) [Pubmed]
  32. Overexpression of CXCL10 in human prostate LNCaP cells activates its receptor (CXCR3) expression and inhibits cell proliferation. Nagpal, M.L., Davis, J., Lin, T. Biochim. Biophys. Acta (2006) [Pubmed]
  33. CXCL10 production from cytomegalovirus-stimulated microglia is regulated by both human and viral interleukin-10. Cheeran, M.C., Hu, S., Sheng, W.S., Peterson, P.K., Lokensgard, J.R. J. Virol. (2003) [Pubmed]
  34. Adenosine affects expression of membrane molecules, cytokine and chemokine release, and the T-cell stimulatory capacity of human dendritic cells. Panther, E., Corinti, S., Idzko, M., Herouy, Y., Napp, M., la Sala, A., Girolomoni, G., Norgauer, J. Blood (2003) [Pubmed]
  35. The relative activity of CXCR3 and CCR5 ligands in T lymphocyte migration: concordant and disparate activities in vitro and in vivo. Stanford, M.M., Issekutz, T.B. J. Leukoc. Biol. (2003) [Pubmed]
  36. Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells. Megjugorac, N.J., Young, H.A., Amrute, S.B., Olshalsky, S.L., Fitzgerald-Bocarsly, P. J. Leukoc. Biol. (2004) [Pubmed]
  37. Lactobacilli and streptococci induce inflammatory chemokine production in human macrophages that stimulates Th1 cell chemotaxis. Veckman, V., Miettinen, M., Matikainen, S., Lande, R., Giacomini, E., Coccia, E.M., Julkunen, I. J. Leukoc. Biol. (2003) [Pubmed]
  38. Endothelial cell-T lymphocyte interactions: iP-10 stimulates rapid transendothelial migration of human effector but not central memory CD4+ T cells. Requirements for shear stress and adhesion molecules. Manes, T.D., Pober, J.S., Kluger, M.S. Transplantation (2006) [Pubmed]
  39. Description of B lymphocytes and plasma cells, complement, and chemokines/receptors in acute liver allograft rejection. Krukemeyer, M.G., Moeller, J., Morawietz, L., Rudolph, B., Neumann, U., Theruvath, T., Neuhaus, P., Krenn, V. Transplantation (2004) [Pubmed]
  40. High Levels of CXCL10 Are Produced by Intestinal Epithelial Cells in AIDS Patients with Active Cryptosporidiosis but Not after Reconstitution of Immunity. Wang, H.C., Dann, S.M., Okhuysen, P.C., Lewis, D.E., Chappell, C.L., Adler, D.G., White, A.C. Infect. Immun. (2007) [Pubmed]
  41. T lymphocyte chemotactic chemokines in acute myelogenous leukemia (AML): local release by native human AML blasts and systemic levels of CXCL10 (IP-10), CCL5 (RANTES) and CCL17 (TARC). Olsnes, A.M., Motorin, D., Ryningen, A., Zaritskey, A.Y., Bruserud, O. Cancer Immunol. Immunother. (2006) [Pubmed]
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