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Gene Review

Cxcl9  -  chemokine (C-X-C motif) ligand 9

Mus musculus

Synonyms: BB139920, C-X-C motif chemokine 9, CMK, Gamma-interferon-induced monokine, MIG, ...
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Disease relevance of Cxcl9

  • In this study, we found that intrapulmonary administration of the gram-negative bacterium Klebsiella pneumoniae resulted in the local and systemic expression of IP-10, followed sequentially by MIG expression [1].
  • Collectively, these results suggest that in the sensitized host, CXCR3, IP-10, and Mig are required for optimal DTH responsiveness but are not essential for containing HSV-1 replication in the ear pinna [2].
  • Immunohistochemistry confirmed that PTLD tissues contain less IL-18 and Mig protein than tissues with infectious mononucleosis [3].
  • Surprisingly, there was no expression in the lungs of mice infected with vaccinia, unlike the elevated expression shown previously for other interferon-regulated chemokines, such as Crg2 and Mig [4].
  • In the present study, murine Mig RNA was found to be expressed at higher levels in regressing Burkitt's lymphoma tumors established in nude mice compared with progressively growing tumors [5].

High impact information on Cxcl9


Chemical compound and disease context of Cxcl9


Biological context of Cxcl9


Anatomical context of Cxcl9


Associations of Cxcl9 with chemical compounds

  • In addition, apigenin inhibits IFNgamma-stimulated secretion of monokines, CXCL-9, and -10 in MC3T3-E1 cells [19].
  • Luciferase reporter assay demonstrated that sulindac inhibited IFNgamma-induced promoter activity of the CXCL9 gene [20].
  • Heparin displaces interferon-gamma-inducible chemokines (IP-10, I-TAC, and Mig) sequestered in the vasculature and inhibits the transendothelial migration and arterial recruitment of T cells [21].
  • In contrast, introduction of exogenous CXCL9 into the airway at the time of allergen challenge dramatically reduced airway hyper-reactivity and eosinophil accumulation [22].
  • In contrast to SEB administration, treatment with lipopolysaccharide resulted in a strong induction of IP-10 and Mig in IFN-gamma receptor-deficient mice [23].

Regulatory relationships of Cxcl9

  • Interestingly, our experiments also revealed a critical role for NF-kappaB in mediating IFN-gamma-induced MIG expression independent of HA [24].
  • Anti-CXCL9/Mig was administered for 2 weeks post-transplant to determine whether impairment of activated T-cell migration could further prolong cardiac allograft survival in plt recipients [11].
  • This study demonstrates that MIG/CXCL9 stimulates T lymphocyte proliferation and effector cytokine production, in addition to its chemotactic effects [15].
  • Xenografts showed stronger interferon (IFN)-inducible 10-kDa protein (IP-10) and monokine induced by IFN (MIG) mRNA expression levels, which appeared earlier than in the allografts [25].
  • Collectively, these data indicate that Mig is important in contributing to host defense by promoting a protective Th1 response against viral infection of the CNS [12].

Other interactions of Cxcl9

  • The increase in MIG expression by RANKL was confirmed by reverse transcription-polymerase chain reaction and Western blot analysis [26].
  • 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 [27].
  • 3) Interferon-gamma neutralization profoundly abrogated MIG, but had little effect on other CKs [28].
  • We found that in the spleen and liver MIP-1alpha, MIP-2 and Mig were the predominant chemokines expressed [29].
  • In contrast, message expression of gamma interferon, MIG, IP-10, and I-TAC peaked at 2 days [30].

Analytical, diagnostic and therapeutic context of Cxcl9


  1. 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]
  2. CXCR3, IP-10, and Mig are required for CD4+ T cell recruitment during the DTH response to HSV-1 yet are independent of the mechanism for viral clearance. Molesworth-Kenyon, S., Mates, A., Yin, R., Strieter, R., Oakes, J., Lausch, R. Virology (2005) [Pubmed]
  3. Interleukin-18, interferon-gamma, IP-10, and Mig expression in Epstein-Barr virus-induced infectious mononucleosis and posttransplant lymphoproliferative disease. Setsuda, J., Teruya-Feldstein, J., Harris, N.L., Ferry, J.A., Sorbara, L., Gupta, G., Jaffe, E.S., Tosato, G. Am. J. Pathol. (1999) [Pubmed]
  4. A recombinant vaccinia virus encoding the interferon-inducible T-cell alpha chemoattractant is attenuated in vivo. Hamilton, N.H., Mahalingam, S., Banyer, J.L., Ramshaw, I.A., Thomson, S.A. Scand. J. Immunol. (2004) [Pubmed]
  5. Mig, the monokine induced by interferon-gamma, promotes tumor necrosis in vivo. Sgadari, C., Farber, J.M., Angiolillo, A.L., Liao, F., Teruya-Feldstein, J., Burd, P.R., Yao, L., Gupta, G., Kanegane, C., Tosato, G. Blood (1997) [Pubmed]
  6. Tumor necrosis factor-dependent segmental control of MIG expression by high endothelial venules in inflamed lymph nodes regulates monocyte recruitment. Janatpour, M.J., Hudak, S., Sathe, M., Sedgwick, J.D., McEvoy, L.M. J. Exp. Med. (2001) [Pubmed]
  7. Blocking chemokine responsive to gamma-2/interferon (IFN)-gamma inducible protein and monokine induced by IFN-gamma activity in vivo reduces the pathogenetic but not the antiviral potential of hepatitis B virus-specific cytotoxic T lymphocytes. Kakimi, K., Lane, T.E., Wieland, S., Asensio, V.C., Campbell, I.L., Chisari, F.V., Guidotti, L.G. J. Exp. Med. (2001) [Pubmed]
  8. 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]
  9. The CXCR3 activating chemokines IP-10, Mig, and IP-9 are expressed in allergic but not in irritant patch test reactions. Flier, J., Boorsma, D.M., Bruynzeel, D.P., Van Beek, P.J., Stoof, T.J., Scheper, R.J., Willemze, R., Tensen, C.P. J. Invest. Dermatol. (1999) [Pubmed]
  10. Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by IFN-gamma (Mig, CXCL9). Fulkerson, P.C., Zimmermann, N., Brandt, E.B., Muntel, E.E., Doepker, M.P., Kavanaugh, J.L., Mishra, A., Witte, D.P., Zhang, H., Farber, J.M., Yang, M., Foster, P.S., Rothenberg, M.E. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  11. CXCL9 antagonism further extends prolonged cardiac allograft survival in CCL19/CCL21-deficient mice. Colvin, B.L., Wang, Z., Nakano, H., Wu, W., Kakiuchi, T., Fairchild, R.L., Thomson, A.W. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2005) [Pubmed]
  12. Expression of Mig (monokine induced by interferon-gamma) is important in T lymphocyte recruitment and host defense following viral infection of the central nervous system. Liu, M.T., Armstrong, D., Hamilton, T.A., Lane, T.E. J. Immunol. (2001) [Pubmed]
  13. Candidate genes associated with tumor regression mediated by intratumoral IL-12 electroporation gene therapy. Li, S., Xia, X., Mellieon, F.M., Liu, J., Steele, S. Mol. Ther. (2004) [Pubmed]
  14. IFN-gamma-inducible chemokines enhance adaptive immunity and colitis. Singh, U.P., Singh, S., Iqbal, N., Weaver, C.T., McGhee, J.R., Lillard, J.W. J. Interferon Cytokine Res. (2003) [Pubmed]
  15. Chemokine monokine induced by IFN-gamma/CXC chemokine ligand 9 stimulates T lymphocyte proliferation and effector cytokine production. Whiting, D., Hsieh, G., Yun, J.J., Banerji, A., Yao, W., Fishbein, M.C., Belperio, J., Strieter, R.M., Bonavida, B., Ardehali, A. J. Immunol. (2004) [Pubmed]
  16. 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]
  17. Differential effects of ageing on cytokine and chemokine responses during type-1 (mycobacterial) and type-2 (schistosomal) pulmonary granulomatous inflammation in mice. Chiu, B.C., Shang, X., Frait, K.A., Hu, J.S., Komuniecki, E., Miller, R.A., Chensue, S.W. Mech. Ageing Dev. (2002) [Pubmed]
  18. Regulated production of interferon-inducible T-cell chemoattractants by human intestinal epithelial cells. Dwinell, M.B., Lügering, N., Eckmann, L., Kagnoff, M.F. Gastroenterology (2001) [Pubmed]
  19. Attenuation of osteoclastogenesis and osteoclast function by apigenin. Bandyopadhyay, S., Lion, J.M., Mentaverri, R., Ricupero, D.A., Kamel, S., Romero, J.R., Chattopadhyay, N. Biochem. Pharmacol. (2006) [Pubmed]
  20. Sulindac, a nonsteroidal anti-inflammatory drug, selectively inhibits interferon-gamma-induced expression of the chemokine CXCL9 gene in mouse macrophages. Sakaeda, Y., Hiroi, M., Shimojima, T., Iguchi, M., Kanegae, H., Ohmori, Y. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  21. Heparin displaces interferon-gamma-inducible chemokines (IP-10, I-TAC, and Mig) sequestered in the vasculature and inhibits the transendothelial migration and arterial recruitment of T cells. Ranjbaran, H., Wang, Y., Manes, T.D., Yakimov, A.O., Akhtar, S., Kluger, M.S., Pober, J.S., Tellides, G. Circulation (2006) [Pubmed]
  22. Regulation of cockroach antigen-induced allergic airway hyperreactivity by the CXCR3 ligand CXCL9. Thomas, M.S., Kunkel, S.L., Lukacs, N.W. J. Immunol. (2004) [Pubmed]
  23. Distinct functions of interferon-gamma for chemokine expression in models of acute lung inflammation. Neumann, B., Emmanuilidis, K., Stadler, M., Holzmann, B. Immunology (1998) [Pubmed]
  24. NF-kappa B activation mediates the cross-talk between extracellular matrix and interferon-gamma (IFN-gamma) leading to enhanced monokine induced by IFN-gamma (MIG) expression in macrophages. Horton, M.R., Boodoo, S., Powell, J.D. J. Biol. Chem. (2002) [Pubmed]
  25. 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]
  26. Monokine induced by interferon-gamma is induced by receptor activator of nuclear factor kappa B ligand and is involved in osteoclast adhesion and migration. Kwak, H.B., Lee, S.W., Jin, H.M., Ha, H., Lee, S.H., Takeshita, S., Tanaka, S., Kim, H.M., Kim, H.H., Lee, Z.H. Blood (2005) [Pubmed]
  27. 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]
  28. Chemokine expression dynamics in mycobacterial (type-1) and schistosomal (type-2) antigen-elicited pulmonary granuloma formation. Qiu, B., Frait, K.A., Reich, F., Komuniecki, E., Chensue, S.W. Am. J. Pathol. (2001) [Pubmed]
  29. T cell infiltration and chemokine expression: relevance to the disease localization in murine graft-versus-host disease. New, J.Y., Li, B., Koh, W.P., Ng, H.K., Tan, S.Y., Yap, E.H., Chan, S.H., Hu, H.Z. Bone Marrow Transplant. (2002) [Pubmed]
  30. CXCR3 and its ligands participate in the host response to Bordetella bronchiseptica infection of the mouse respiratory tract but are not required for clearance of bacteria from the lung. Widney, D.P., Hu, Y., Foreman-Wykert, A.K., Bui, K.C., Nguyen, T.T., Lu, B., Gerard, C., Miller, J.F., Smith, J.B. Infect. Immun. (2005) [Pubmed]
  31. Changes in the transcriptome in allograft rejection: IFN-gamma-induced transcripts in mouse kidney allografts. Famulski, K.S., Einecke, G., Reeve, J., Ramassar, V., Allanach, K., Mueller, T., Hidalgo, L.G., Zhu, L.F., Halloran, P.F. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2006) [Pubmed]
  32. Immunotherapy with interleukin-10 depends on the CXC chemokines inducible protein-10 and monokine induced by IFN-gamma. Dorsey, R., Kundu, N., Yang, Q., Tannenbaum, C.S., Sun, H., Hamilton, T.A., Fulton, A.M. Cancer Res. (2002) [Pubmed]
  33. MIG (CXCL9) chemokine gene therapy combines with antibody-cytokine fusion protein to suppress growth and dissemination of murine colon carcinoma. Ruehlmann, J.M., Xiang, R., Niethammer, A.G., Ba, Y., Pertl, U., Dolman, C.S., Gillies, S.D., Reisfeld, R.A. Cancer Res. (2001) [Pubmed]
  34. The role of MIG/CXCL9 in cardiac allograft vasculopathy. Yun, J.J., Fischbein, M.P., Whiting, D., Irie, Y., Fishbein, M.C., Burdick, M.D., Belperio, J., Strieter, R.M., Laks, H., Berliner, J.A., Ardehali, A. Am. J. Pathol. (2002) [Pubmed]
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