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Gene Review

CXCL9  -  chemokine (C-X-C motif) ligand 9

Homo sapiens

Synonyms: C-X-C motif chemokine 9, CMK, Gamma-interferon-induced monokine, HuMIG, Humig, ...
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Disease relevance of CXCL9


Psychiatry related information on CXCL9


High impact information on CXCL9

  • Finally, hrIL-12 strongly reduced the tumorigenicity of IL-12Rbeta2-transfected Burkitt lymphoma RAJI cells in SCID-NOD mice through antiproliferative and proapoptotic effects, coupled with neoangiogenesis inhibition related to human IFN-gamma-independent induction of hMig/CXCL9 [7].
  • Lastly, fresh human IEL constitutively expressed CXCR-3 (the common receptor for IP-10 and MIG), and fresh IEL also exhibited chemotaxis to by rIP-10, rMIG, and epithelial-conditioned media [8].
  • Production of IP-10 and MIG in fresh epithelial cells was supported by in situ hybridization and enzyme-linked immunosorbent assay [8].
  • Variable numbers of pancreas-infiltrating T cells express MIG mRNA [9].
  • The structure of human GzmA bound to a tripeptide CMK inhibitor, determined at a resolution of 2.4 A, reveals that the oligomeric state contributes to substrate selection by limiting access to the active site for potential macromolecular substrates and inhibitors [10].

Chemical compound and disease context of CXCL9


Biological context of CXCL9


Anatomical context of CXCL9


Associations of CXCL9 with chemical compounds

  • In asthmatic patients, the ex vivo release of IP-10 and MIG was attenuated in PBMC activated with allergen, mitogens and IL-18 (p < 0.05) [24].
  • METHODS: The spontaneous and TNF-alpha-stimulated secretion of IL-1beta, IL-8, IP-10 and MIG from HT-29 and Caco-2 cells was tested with, or without pretreatment with allicin [25].
  • The program was carried out via intramuscular delivery of pORF-MIG at 100 mug/mouse twice a week for 4 weeks, and/or intraperitoneal delivery of cisplatin at 0.6 mg/kg/mouse every 3 days for 48 days [12].
  • Outside-In signaling of soluble and solid-phase fibrinogen through integrin alphaIIbbeta3 is different and cooperative with each other in a megakaryoblastic leukemia cell line, CMK [26].
  • This report identifies cDNA for a structurally altered P(2X1)-like receptor in megakaryocytic cell lines (Dami and CMK 11-5) and platelets that, when transfected into nonresponsive 1321 cells, confers a specific sensitivity to ADP with the pharmacologic rank order of ADP > > ATP > > > alpha,beta-methylene-ATP as measured by Ca(++) influx [27].

Regulatory relationships of CXCL9

  • This supports the notion that CXCL9 interaction with cells expressing CXCR3 has an important role in the recruitment of mononuclear cells, a pivotal event in the pathogenesis of acute lung allograft rejection [28].
  • In contrast, inhibition of the constitutive NF-kappaB in HSC-2 cells by adenovirus-mediated gene transfer of a dominant-negative IkappaBalpha suppressed the IFNgamma-induced expression of the CXCL9 and CXCL10 mRNAs [29].
  • We conclude that MIG production correlates significantly with enhanced T-cell IFN-gamma production induced by M. tuberculosis-specific antigens ESAT-6/CFP-10 [30].

Other interactions of CXCL9

  • Elevations in CXC ligand 9 (CXCL9), CXCL10, and CXCL11 were observed in all patients with HCV [31].
  • Levels of CXCL10 and CXCL9 decreased following successful antiviral therapy; CXCL11 did not decline significantly during or in the first 6 months after therapy [31].
  • Systemic CXCL9 levels decreased from pre- to grass pollen season in allergics (P < 0.05), whereas CCL17 decreased in non-allergics (P < 0.05) over the same period [32].
  • Gelatinase B degrades IP-10 and cleaves MIG at three different sites in its extended carboxyterminal region [23].
  • Levels of TARC, MDC, and MIG were significantly decreased after treatment when the skin lesions disappeared in these patients [33].

Analytical, diagnostic and therapeutic context of CXCL9

  • In this study, we demonstrate that CXCL9 and CXCL10 are up-regulated in unique patterns following tracheal transplantation in mice [34].
  • Quantitative real-time PCR confirmed these findings and revealed up-regulated mRNA levels of another chemoattractant that activates CXCR3, monokine induced by IFN-gamma (Mig; CXCL9) [35].
  • Prediction of acute renal allograft rejection by urinary monokine induced by IFN-gamma (MIG) [36].
  • In pH-adjusted urine, MIG and IP-10 were determined by modified ELISA [36].
  • MIG values indicated both imminent rejection and response to successful antirejection therapy [36].


  1. 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]
  2. The CXC Chemokine MIG/CXCL9 Is Important in Innate Immunity against Streptococcus pyogenes. Egesten, A., Eliasson, M., Johansson, H.M., Olin, A.I., Morgelin, M., Mueller, A., Pease, J.E., Frick, I.M., Bjorck, L. J. Infect. Dis. (2007) [Pubmed]
  3. Increased serum concentrations of monokine induced by interferon-gamma/CXCL9 and interferon-gamma-inducible protein 10/CXCL-10 in Sydenham's chorea patients. Teixeira, A.L., Cardoso, F., Souza, A.L., Teixeira, M.M. J. Neuroimmunol. (2004) [Pubmed]
  4. Role for interferon-gamma inducible chemokines in endocrine autoimmunity: an expanding field. Rotondi, M., Lazzeri, E., Romagnani, P., Serio, M. J. Endocrinol. Invest. (2003) [Pubmed]
  5. 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]
  6. Efficacy of telephone and mail intervention in patient compliance with antihypertensive drugs in hypertension. ETECUM-HTA study. Contreras, E.M., García, O.V., Claros, N.M., Guillén, V.G., de la Figuera von Wichmann, M., Martínez, J.J., Fernández, R. Blood Press. (2005) [Pubmed]
  7. The IL-12Rbeta2 gene functions as a tumor suppressor in human B cell malignancies. Airoldi, I., Di Carlo, E., Banelli, B., Moserle, L., Cocco, C., Pezzolo, A., Sorrentino, C., Rossi, E., Romani, M., Amadori, A., Pistoia, V. J. Clin. Invest. (2004) [Pubmed]
  8. Characterization of epithelial chemoattractants for human intestinal intraepithelial lymphocytes. Shibahara, T., Wilcox, J.N., Couse, T., Madara, J.L. Gastroenterology (2001) [Pubmed]
  9. Differential expression of chemokines in normal pancreas and in chronic pancreatitis. Saurer, L., Reber, P., Schaffner, T., Büchler, M.W., Buri, C., Kappeler, A., Walz, A., Friess, H., Mueller, C. Gastroenterology (2000) [Pubmed]
  10. The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity. Bell, J.K., Goetz, D.H., Mahrus, S., Harris, J.L., Fletterick, R.J., Craik, C.S. Nat. Struct. Biol. (2003) [Pubmed]
  11. The role of CXC chemokines as regulators of angiogenesis. Strieter, R.M., Polverini, P.J., Arenberg, D.A., Kunkel, S.L. Shock (1995) [Pubmed]
  12. Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma. Zhang, R., Tian, L., Chen, L.J., Xiao, F., Hou, J.M., Zhao, X., Li, G., Yao, B., Wen, Y.J., Li, J., Zhang, L., Chen, X.C., Luo, F., Peng, F., Jiang, Y., Wei, Y.Q. Gene Ther. (2006) [Pubmed]
  13. IL-3 and ribavirin induce differentiation and growth suppression during long-term treatment of a megakaryocytic leukemia cell line. Majumdar, A., Kerby, S., Mullikin, B., Beckstead, J.H., Stenberg, P.E., Seidman, M.M. J. Cell. Physiol. (1995) [Pubmed]
  14. Modulation of ara-CTP levels by fludarabine and hydroxyurea in leukemic cells. Ahlmann, M., Lanvers, C., Lümkemann, K., Rössig, C., Freund, A., Baumann, M., Boos, J. Leukemia (2001) [Pubmed]
  15. Differential expression of CCR3 and CXCR3 by human lung and bone marrow-derived mast cells: implications for tissue mast cell migration. Brightling, C.E., Kaur, D., Berger, P., Morgan, A.J., Wardlaw, A.J., Bradding, P. J. Leukoc. Biol. (2005) [Pubmed]
  16. Evaluation of CXCL9 and CXCL10 as circulating biomarkers of human cardiac allograft rejection. Karason, K., Jernås, M., Hägg, D.A., Svensson, P.A. BMC cardiovascular disorders [electronic resource]. (2006) [Pubmed]
  17. Infiltration of Th1 and Th2 lymphocytes around Hodgkin and Reed-Sternberg (H&RS) cells in Hodgkin disease: Relation with expression of CXC and CC chemokines on H&RS cells. Ohshima, K., Tutiya, T., Yamaguchi, T., Suzuki, K., Suzumiya, J., Kawasaki, C., Haraoka, S., Kikuchi, M. Int. J. Cancer (2002) [Pubmed]
  18. Localization of the human CXC chemokine subfamily on the long arm of chromosome 4 using radiation hybrids. Modi, W.S., Chen, Z.Q. Genomics (1998) [Pubmed]
  19. Classification of distinct subtypes of peripheral T-cell lymphoma unspecified, identified by chemokine and chemokine receptor expression: Analysis of prognosis. Ohshima, K., Karube, K., Kawano, R., Tsuchiya, T., Suefuji, H., Yamaguchi, T., Suzumiya, J., Kikuchii, M. Int. J. Oncol. (2004) [Pubmed]
  20. Expression of IP-10/CXCL10 and MIG/CXCL9 in the thyroid and increased levels of IP-10/CXCL10 in the serum of patients with recent-onset Graves' disease. Romagnani, P., Rotondi, M., Lazzeri, E., Lasagni, L., Francalanci, M., Buonamano, A., Milani, S., Vitti, P., Chiovato, L., Tonacchera, M., Bellastella, A., Serio, M. Am. J. Pathol. (2002) [Pubmed]
  21. TLR ligands and cytokines induce CXCR3 ligands in endothelial cells: enhanced CXCL9 in autoimmune arthritis. Loos, T., Dekeyzer, L., Struyf, S., Schutyser, E., Gijsbers, K., Gouwy, M., Fraeyman, A., Put, W., Ronsse, I., Grillet, B., Opdenakker, G., Damme, J.V., Proost, P. Lab. Invest. (2006) [Pubmed]
  22. Human eosinophils produce the T cell-attracting chemokines MIG and IP-10 upon stimulation with IFN-gamma. Dajotoy, T., Andersson, P., Bjartell, A., Löfdahl, C.G., Tapper, H., Egesten, A. J. Leukoc. Biol. (2004) [Pubmed]
  23. Carboxyterminal cleavage of the chemokines MIG and IP-10 by gelatinase B and neutrophil collagenase. Van den Steen, P.E., Husson, S.J., Proost, P., Van Damme, J., Opdenakker, G. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  24. Aberrant expression of CC and CXC chemokines and their receptors in patients with asthma. Lun, S.W., Wong, C.K., Ko, F.W., Ip, W.K., Hui, D.S., Lam, C.W. J. Clin. Immunol. (2006) [Pubmed]
  25. Allicin inhibits spontaneous and TNF-alpha induced secretion of proinflammatory cytokines and chemokines from intestinal epithelial cells. Lang, A., Lahav, M., Sakhnini, E., Barshack, I., Fidder, H.H., Avidan, B., Bardan, E., Hershkoviz, R., Bar-Meir, S., Chowers, Y. Clinical nutrition (Edinburgh, Scotland) (2004) [Pubmed]
  26. Outside-In signaling of soluble and solid-phase fibrinogen through integrin alphaIIbbeta3 is different and cooperative with each other in a megakaryoblastic leukemia cell line, CMK. Tohyama, Y., Tohyama, K., Tsubokawa, M., Asahi, M., Yoshida, Y., Yamamura, H. Blood (1998) [Pubmed]
  27. Novel structurally altered P(2X1) receptor is preferentially activated by adenosine diphosphate in platelets and megakaryocytic cells. Greco, N.J., Tonon, G., Chen, W., Luo, X., Dalal, R., Jamieson, G.A. Blood (2001) [Pubmed]
  28. Role of CXCL9/CXCR3 chemokine biology during pathogenesis of acute lung allograft rejection. Belperio, J.A., Keane, M.P., Burdick, M.D., Lynch, J.P., Zisman, D.A., Xue, Y.Y., Li, K., Ardehali, A., Ross, D.J., Strieter, R.M. J. Immunol. (2003) [Pubmed]
  29. Constitutive nuclear factor kappaB activity is required to elicit interferon-gamma-induced expression of chemokine CXC ligand 9 (CXCL9) and CXCL10 in human tumour cell lines. Hiroi, M., Ohmori, Y. Biochem. J. (2003) [Pubmed]
  30. Monokine induced by interferon gamma and IFN-gamma response to a fusion protein of Mycobacterium tuberculosis ESAT-6 and CFP-10 in Brazilian tuberculosis patients. Abramo, C., Meijgaarden, K.E., Garcia, D., Franken, K.L., Klein, M.R., Kolk, A.J., Oliveira, S.C., Ottenhoff, T.H., Teixeira, H.C. Microbes Infect. (2006) [Pubmed]
  31. 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]
  32. Systemic chemokine and chemokine receptor responses are divergent in allergic versus non-allergic humans. Campbell, J.D., Stinson, M.J., Simons, F.E., HayGlass, K.T. Int. Immunol. (2002) [Pubmed]
  33. Both Th1 and Th2 chemokines are elevated in sera of patients with autoimmune blistering diseases. Echigo, T., Hasegawa, M., Shimada, Y., Inaoki, M., Takehara, K., Sato, S. Arch. Dermatol. Res. (2006) [Pubmed]
  34. CXCR3 and its ligands in a murine model of obliterative bronchiolitis: regulation and function. Medoff, B.D., Wain, J.C., Seung, E., Jackobek, R., Means, T.K., Ginns, L.C., Farber, J.M., Luster, A.D. J. Immunol. (2006) [Pubmed]
  35. Overexpression of IFN-induced protein 10 and its receptor CXCR3 in myasthenia gravis. Feferman, T., Maiti, P.K., Berrih-Aknin, S., Bismuth, J., Bidault, J., Fuchs, S., Souroujon, M.C. J. Immunol. (2005) [Pubmed]
  36. Prediction of acute renal allograft rejection by urinary monokine induced by IFN-gamma (MIG). Hauser, I.A., Spiegler, S., Kiss, E., Gauer, S., Sichler, O., Scheuermann, E.H., Ackermann, H., Pfeilschifter, J.M., Geiger, H., Gröne, H.J., Radeke, H.H. J. Am. Soc. Nephrol. (2005) [Pubmed]
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