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Gene Review

Cxcl10  -  chemokine (C-X-C motif) ligand 10

Mus musculus

Synonyms: 10 kDa interferon gamma-induced protein, C-X-C motif chemokine 10, C7, CRG-2, Crg2, ...
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Disease relevance of Cxcl10

  • In addition, IP-10(-/-) mice exhibited an impaired contact hypersensitivity response, characterized by decreased ear swelling and reduced inflammatory cell infiltrates [1].
  • T Cell Antiviral Effector Function Is Not Dependent on CXCL10 Following Murine Coronavirus Infection [2].
  • Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus [3].
  • Furthermore, IP-10(-/-) mice infected with a neurotropic mouse hepatitis virus had an impaired ability to control viral replication in the brain [1].
  • CONCLUSION: We prepared a novel potent IP-10 antagonist and demonstrated its ability to ameliorate the progression of autoimmune sialadenitis [4].

Psychiatry related information on Cxcl10


High impact information on Cxcl10


Chemical compound and disease context of Cxcl10

  • Type 1 diabetes is considered to be a Th1-dominant autoimmune disease, and a suppressive effect of CXCL10 neutralization on diabetes development has been reported in a cyclophosphamide-induced accelerated diabetes model through induction of beta cell proliferation [9].
  • We found that IP-10 is highly expressed in a mouse model of pulmonary fibrosis induced by bleomycin [10].
  • To determine whether PPARgamma ligands reduce this inflammation in part by reducing TH1 chemoattractant levels in vivo, the TZD pioglitazone was tested for its effects on a TH1 chemokine (CXCL10) in 2 models of colitis (i.e., dextran sodium sulfate and 2,4,6-dinitrobenzene sulfonic acid-mediated colitis) [11].
  • A series of the C7-substituted A-ring pyrrole derivatives of duocarmycin were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice [12].

Biological context of Cxcl10


Anatomical context of Cxcl10


Associations of Cxcl10 with chemical compounds

  • Indeed, the Trif-dependent gene cxcl10 was not expressed in ECs after LPS stimulation [20].
  • First, LPS-induced IP-10 mRNA expression was blocked in cells cotreated with cycloheximide [21].
  • Our experiments demonstrate that IP-10 is up-regulated in the lung after allergen challenge [22].
  • Crg-2 expression was noted in vivo in multiple models of hepatic and bile duct injury, including bile duct ligation and CCl(4), D-galactosamine, and methylene dianiline toxic liver injuries [23].
  • In contrast, IVAG administration of R-848 resulted in high levels of plasma IP-10, similar to those seen after parenteral administration, but overall, weaker or shorter-lived local immune responses than obtained with CpG ODN [24].

Physical interactions of Cxcl10

  • The inhibitory effect of CXCL10/IP-10 on the binding of dengue virus to cells may represent a novel contribution of this chemokine to the host defense against viral infection [25].
  • TNF-alpha at doses up to 10 ng/ml and soluble immune complexes up to 150 micrograms/ml antibody evoked 3- to 5-fold increases in IP-10 mRNA expression, much less than the 30- to 70-fold increases seen with IFN-gamma and LPS [26].

Regulatory relationships of Cxcl10


Other interactions of Cxcl10

  • The in vivo neutralization of either Mig or IP-10 significantly reduced the severity of IPS compared with control-treated animals, and an additive effect was observed when both ligands were blocked simultaneously [30].
  • MCP-1, IP-10, and MIP-2 RNA expression significantly correlated with clinical score [31].
  • Chemokine CXCL10 (IP-10) is sufficient to trigger an immune response to injected antigens in a mouse model [32].
  • TNFR1-/- mice with EAE had significantly higher expression of CXCL10 mRNA (but not CCL5 mRNA) in the CNS compared to WT mice with EAE [33].
  • RESULTS: Cytokine-treated WT islets demonstrated an increase in IRF-1 and iNOS gene expression, inhibition of GSIR, increased rates of apoptosis, and increased gene transcription and protein release for IP-10 and MCP-1 [16].

Analytical, diagnostic and therapeutic context of Cxcl10

  • Donor-derived IP-10 initiates development of acute allograft rejection [17].
  • These data emphasize the pivotal role of donor-derived IP-10 in initiating alloresponses, with implications for tissue engineering to decrease immunogenicity, and demonstrate that chemokine redundancy may not be operative in vivo [17].
  • In the present study, we report that targeted deletion of IP-10 did not diminish the expression, severity, or histopathology of EAE induced by active immunization with 100 micro g of myelin oligodendrocyte glycoprotein peptide (MOG)p35-55 [13].
  • Analysis of IP-10 mRNA distribution in the liver and kidney by in situ hybridization indicated that expression in both tissues was most prominent in the reticuloendothelial cell system, particularly in the endothelial lining of the microvascular circulation [14].
  • Induction of Crg-2 was also examined following two-thirds hepatectomy, a model that minimally injures the remaining liver, but that requires a large hepatic regenerative response [23].


  1. IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. Dufour, J.H., Dziejman, M., Liu, M.T., Leung, J.H., Lane, T.E., Luster, A.D. J. Immunol. (2002) [Pubmed]
  2. T Cell Antiviral Effector Function Is Not Dependent on CXCL10 Following Murine Coronavirus Infection. Stiles, L.N., Hardison, J.L., Schaumburg, C.S., Whitman, L.M., Lane, T.E. J. Immunol. (2006) [Pubmed]
  3. Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus. Hsieh, M.F., Lai, S.L., Chen, J.P., Sung, J.M., Lin, Y.L., Wu-Hsieh, B.A., Gerard, C., Luster, A., Liao, F. J. Immunol. (2006) [Pubmed]
  4. Antagonist of interferon-inducible protein 10/CXCL10 ameliorates the progression of autoimmune sialadenitis in MRL/lpr mice. Hasegawa, H., Inoue, A., Kohno, M., Muraoka, M., Miyazaki, T., Terada, M., Nakayama, T., Yoshie, O., Nose, M., Yasukawa, M. Arthritis Rheum. (2006) [Pubmed]
  5. CXC chemokine ligand 10 controls viral infection in the central nervous system: evidence for a role in innate immune response through recruitment and activation of natural killer cells. Trifilo, M.J., Montalto-Morrison, C., Stiles, L.N., Hurst, K.R., Hardison, J.L., Manning, J.E., Masters, P.S., Lane, T.E. J. Virol. (2004) [Pubmed]
  6. IP-10 is critical for effector T cell trafficking and host survival in Toxoplasma gondii infection. Khan, I.A., MacLean, J.A., Lee, F.S., Casciotti, L., DeHaan, E., Schwartzman, J.D., Luster, A.D. Immunity (2000) [Pubmed]
  7. Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation. Okabe, Y., Kawane, K., Akira, S., Taniguchi, T., Nagata, S. J. Exp. Med. (2005) [Pubmed]
  8. Pivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes. Yoneyama, H., Narumi, S., Zhang, Y., Murai, M., Baggiolini, M., Lanzavecchia, A., Ichida, T., Asakura, H., Matsushima, K. J. Exp. Med. (2002) [Pubmed]
  9. CXCL10 DNA vaccination prevents spontaneous diabetes through enhanced beta cell proliferation in NOD mice. Shigihara, T., Shimada, A., Oikawa, Y., Yoneyama, H., Kanazawa, Y., Okubo, Y., Matsushima, K., Yamato, E., Miyazaki, J., Kasuga, A., Saruta, T., Narumi, S. J. Immunol. (2005) [Pubmed]
  10. Inhibition of pulmonary fibrosis by the chemokine IP-10/CXCL10. Tager, A.M., Kradin, R.L., LaCamera, P., Bercury, S.D., Campanella, G.S., Leary, C.P., Polosukhin, V., Zhao, L.H., Sakamoto, H., Blackwell, T.S., Luster, A.D. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  11. Intestinal antiinflammatory effects of thiazolidenedione peroxisome proliferator-activated receptor-gamma ligands on T helper type 1 chemokine regulation include nontranscriptional control mechanisms. Schaefer, K.L., Denevich, S., Ma, C., Cooley, S.R., Nakajima, A., Wada, K., Schlezinger, J., Sherr, D., Saubermann, L.J. Inflamm. Bowel Dis. (2005) [Pubmed]
  12. Synthesis and antitumor activity of duocarmycin derivatives: modification at the C-7 position of segment-A of A-ring pyrrole compounds. Amishiro, N., Okamoto, A., Okabe, M., Saito, H. Bioorg. Med. Chem. (2000) [Pubmed]
  13. IFN-inducible protein 10/CXC chemokine ligand 10-independent induction of experimental autoimmune encephalomyelitis. Klein, R.S., Izikson, L., Means, T., Gibson, H.D., Lin, E., Sobel, R.A., Weiner, H.L., Luster, A.D. J. Immunol. (2004) [Pubmed]
  14. Tissue-specific expression of murine IP-10 mRNA following systemic treatment with interferon gamma. Narumi, S., Wyner, L.M., Stoler, M.H., Tannenbaum, C.S., Hamilton, T.A. J. Leukoc. Biol. (1992) [Pubmed]
  15. Interferon-inducible protein 10, but not monokine induced by gamma interferon, promotes protective type 1 immunity in murine Klebsiella pneumoniae pneumonia. Zeng, X., Moore, T.A., Newstead, M.W., Deng, J.C., Kunkel, S.L., Luster, A.D., Standiford, T.J. Infect. Immun. (2005) [Pubmed]
  16. 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]
  17. Donor-derived IP-10 initiates development of acute allograft rejection. Hancock, W.W., Gao, W., Csizmadia, V., Faia, K.L., Shemmeri, N., Luster, A.D. J. Exp. Med. (2001) [Pubmed]
  18. Hyaluronan fragments synergize with interferon-gamma to induce the C-X-C chemokines mig and interferon-inducible protein-10 in mouse macrophages. Horton, M.R., McKee, C.M., Bao, C., Liao, F., Farber, J.M., Hodge-DuFour, J., Puré, E., Oliver, B.L., Wright, T.M., Noble, P.W. J. Biol. Chem. (1998) [Pubmed]
  19. Among CXCR3 chemokines, IFN-gamma-inducible protein of 10 kDa (CXC chemokine ligand (CXCL) 10) but not monokine induced by IFN-gamma (CXCL9) imprints a pattern for the subsequent development of autoimmune disease. Christen, U., McGavern, D.B., Luster, A.D., von Herrath, M.G., Oldstone, M.B. J. Immunol. (2003) [Pubmed]
  20. Absence of TRAM restricts Toll-like receptor 4 signaling in vascular endothelial cells to the MyD88 pathway. Harari, O.A., Alcaide, P., Ahl, D., Luscinskas, F.W., Liao, J.K. Circ. Res. (2006) [Pubmed]
  21. Interleukin-10 suppresses IP-10 gene transcription by inhibiting the production of class I interferon. Tebo, J.M., Kim, H.S., Gao, J., Armstrong, D.A., Hamilton, T.A. Blood (1998) [Pubmed]
  22. IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma. Medoff, B.D., Sauty, A., Tager, A.M., Maclean, J.A., Smith, R.N., Mathew, A., Dufour, J.H., Luster, A.D. J. Immunol. (2002) [Pubmed]
  23. Cytokine-responsive gene-2/IFN-inducible protein-10 expression in multiple models of liver and bile duct injury suggests a role in tissue regeneration. Koniaris, L.G., Zimmers-Koniaris, T., Hsiao, E.C., Chavin, K., Sitzmann, J.V., Farber, J.M. J. Immunol. (2001) [Pubmed]
  24. Treatment of intravaginal HSV-2 infection in mice: a comparison of CpG oligodeoxynucleotides and resiquimod (R-848). McCluskie, M.J., Cartier, J.L., Patrick, A.J., Sajic, D., Weeratna, R.D., Rosenthal, K.L., Davis, H.L. Antiviral Res. (2006) [Pubmed]
  25. Dengue virus induces expression of CXC chemokine ligand 10/IFN-gamma-inducible protein 10, which competitively inhibits viral binding to cell surface heparan sulfate. Chen, J.P., Lu, H.L., Lai, S.L., Campanella, G.S., Sung, J.M., Lu, M.Y., Wu-Hsieh, B.A., Lin, Y.L., Lane, T.E., Luster, A.D., Liao, F. J. Immunol. (2006) [Pubmed]
  26. Expression of IP-10, a lipopolysaccharide- and interferon-gamma-inducible protein, in murine mesangial cells in culture. Gómez-Chiarri, M., Hamilton, T.A., Egido, J., Emancipator, S.N. Am. J. Pathol. (1993) [Pubmed]
  27. Early up-regulation of CXC-chemokine expression is associated with strong cellular immune responses to murine skin xenografts. Lee, E.M., Park, J.O., Kim, D., Kim, J.Y., Oh, K.H., Park, C.G., Oh, B.H., Kim, S., Ahn, C. Xenotransplantation (2006) [Pubmed]
  28. CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system. Christensen, J.E., de Lemos, C., Moos, T., Christensen, J.P., Thomsen, A.R. J. Immunol. (2006) [Pubmed]
  29. TLR agonists induce regulatory dendritic cells to recruit Th1 cells via preferential IP-10 secretion and inhibit Th1 proliferation. Qian, C., An, H., Yu, Y., Liu, S., Cao, X. Blood (2007) [Pubmed]
  30. Blockade of CXCR3 receptor:ligand interactions reduces leukocyte recruitment to the lung and the severity of experimental idiopathic pneumonia syndrome. Hildebrandt, G.C., Corrion, L.A., Olkiewicz, K.M., Lu, B., Lowler, K., Duffner, U.A., Moore, B.B., Kuziel, W.A., Liu, C., Cooke, K.R. J. Immunol. (2004) [Pubmed]
  31. Modulation of experimental autoimmune encephalomyelitis: effect of altered peptide ligand on chemokine and chemokine receptor expression. Fischer, F.R., Santambrogio, L., Luo, Y., Berman, M.A., Hancock, W.W., Dorf, M.E. J. Neuroimmunol. (2000) [Pubmed]
  32. Chemokine CXCL10 (IP-10) is sufficient to trigger an immune response to injected antigens in a mouse model. Krathwohl, M.D., Anderson, J.L. Vaccine (2006) [Pubmed]
  33. Elevated interferon gamma expression in the central nervous system of tumour necrosis factor receptor 1-deficient mice with experimental autoimmune encephalomyelitis. Wheeler, R.D., Zehntner, S.P., Kelly, L.M., Bourbonnière, L., Owens, T. Immunology (2006) [Pubmed]
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